SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function
Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizop...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Bae, Mihyun [verfasserIn] Roh, Junyeop Daniel [verfasserIn] Kim, Youjoung [verfasserIn] Kim, Seong Soon [verfasserIn] Han, Hye Min [verfasserIn] Yang, Esther [verfasserIn] Kang, Hyojin [verfasserIn] Lee, Suho [verfasserIn] Kim, Jin Yong [verfasserIn] Kang, Ryeonghwa [verfasserIn] Jung, Hwajin [verfasserIn] Yoo, Taesun [verfasserIn] Kim, Hyosang [verfasserIn] Kim, Doyoun [verfasserIn] Oh, Heejeong [verfasserIn] Han, Sungwook [verfasserIn] Kim, Dayeon [verfasserIn] Han, Jinju [verfasserIn] Bae, Yong Chul [verfasserIn] Kim, Hyun [verfasserIn] Ahn, Sunjoo [verfasserIn] Chan, Andrew M [verfasserIn] Lee, Daeyoup [verfasserIn] Kim, Jin Woo [verfasserIn] Kim, Eunjoon [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2021 |
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| Übergeordnetes Werk: |
Enthalten in: EMBO Molecular Medicine - Nature Publishing Group UK, 2023, 13(2021), 2 vom: 11. Jan. |
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| Übergeordnetes Werk: |
volume:13 ; year:2021 ; number:2 ; day:11 ; month:01 |
| Links: |
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| DOI / URN: |
10.15252/emmm.202012632 |
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| Katalog-ID: |
SPR058031278 |
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| 024 | 7 | |a 10.15252/emmm.202012632 |2 doi | |
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| 035 | |a (SPR)emmm.202012632-e | ||
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| 041 | |a eng | ||
| 100 | 1 | |a Bae, Mihyun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © The Author(s) 2021 | ||
| 520 | |a Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction. | ||
| 520 | |a Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function. | ||
| 520 | |a Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. | ||
| 650 | 4 | |a glycine transporter |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a neuropsychiatric disorders |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a NMDA receptor |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a PTEN |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Slc6a20 |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Roh, Junyeop Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Youjoung |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Seong Soon |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Hye Min |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Hyojin |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Suho |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Jin Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Ryeonghwa |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Hwajin |e verfasserin |4 aut | |
| 700 | 1 | |a Yoo, Taesun |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hyosang |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Doyoun |e verfasserin |0 (orcid)0000-0002-6036-8996 |4 aut | |
| 700 | 1 | |a Oh, Heejeong |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Sungwook |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Dayeon |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Jinju |e verfasserin |0 (orcid)0000-0003-1844-2301 |4 aut | |
| 700 | 1 | |a Bae, Yong Chul |e verfasserin |0 (orcid)0000-0002-7618-418X |4 aut | |
| 700 | 1 | |a Kim, Hyun |e verfasserin |0 (orcid)0000-0001-8235-7553 |4 aut | |
| 700 | 1 | |a Ahn, Sunjoo |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Andrew M |e verfasserin |0 (orcid)0000-0001-9923-5464 |4 aut | |
| 700 | 1 | |a Lee, Daeyoup |e verfasserin |0 (orcid)0000-0003-2006-1823 |4 aut | |
| 700 | 1 | |a Kim, Jin Woo |e verfasserin |0 (orcid)0000-0003-0767-1918 |4 aut | |
| 700 | 1 | |a Kim, Eunjoon |e verfasserin |0 (orcid)0000-0001-5518-6584 |4 aut | |
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| 856 | 4 | 0 | |u https://dx.doi.org/10.15252/emmm.202012632 |m X:SPRINGER |x Resolving-System |z kostenfrei |3 Volltext |
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| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
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| 912 | |a GBV_ILN_2034 | ||
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| 912 | |a GBV_ILN_2050 | ||
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| 912 | |a GBV_ILN_2056 | ||
| 912 | |a GBV_ILN_2057 | ||
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| 912 | |a GBV_ILN_2061 | ||
| 912 | |a GBV_ILN_2064 | ||
| 912 | |a GBV_ILN_2068 | ||
| 912 | |a GBV_ILN_2088 | ||
| 912 | |a GBV_ILN_2093 | ||
| 912 | |a GBV_ILN_2106 | ||
| 912 | |a GBV_ILN_2108 | ||
| 912 | |a GBV_ILN_2110 | ||
| 912 | |a GBV_ILN_2111 | ||
| 912 | |a GBV_ILN_2118 | ||
| 912 | |a GBV_ILN_2122 | ||
| 912 | |a GBV_ILN_2129 | ||
| 912 | |a GBV_ILN_2143 | ||
| 912 | |a GBV_ILN_2144 | ||
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| 912 | |a GBV_ILN_2470 | ||
| 912 | |a GBV_ILN_2507 | ||
| 912 | |a GBV_ILN_2522 | ||
| 912 | |a GBV_ILN_2548 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4029 | ||
| 912 | |a GBV_ILN_4035 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4046 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4116 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4155 | ||
| 912 | |a GBV_ILN_4242 | ||
| 912 | |a GBV_ILN_4246 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4251 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
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| 912 | |a GBV_ILN_4313 | ||
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10.15252/emmm.202012632 doi (DE-627)SPR058031278 (SPR)emmm.202012632-e DE-627 ger DE-627 rakwb eng Bae, Mihyun verfasserin aut SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction. Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function. Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. glycine transporter (dpeaa)DE-He213 neuropsychiatric disorders (dpeaa)DE-He213 NMDA receptor (dpeaa)DE-He213 PTEN (dpeaa)DE-He213 Slc6a20 (dpeaa)DE-He213 Roh, Junyeop Daniel verfasserin aut Kim, Youjoung verfasserin aut Kim, Seong Soon verfasserin aut Han, Hye Min verfasserin aut Yang, Esther verfasserin aut Kang, Hyojin verfasserin aut Lee, Suho verfasserin aut Kim, Jin Yong verfasserin aut Kang, Ryeonghwa verfasserin aut Jung, Hwajin verfasserin aut Yoo, Taesun verfasserin aut Kim, Hyosang verfasserin aut Kim, Doyoun verfasserin (orcid)0000-0002-6036-8996 aut Oh, Heejeong verfasserin aut Han, Sungwook verfasserin aut Kim, Dayeon verfasserin aut Han, Jinju verfasserin (orcid)0000-0003-1844-2301 aut Bae, Yong Chul verfasserin (orcid)0000-0002-7618-418X aut Kim, Hyun verfasserin (orcid)0000-0001-8235-7553 aut Ahn, Sunjoo verfasserin aut Chan, Andrew M verfasserin (orcid)0000-0001-9923-5464 aut Lee, Daeyoup verfasserin (orcid)0000-0003-2006-1823 aut Kim, Jin Woo verfasserin (orcid)0000-0003-0767-1918 aut Kim, Eunjoon verfasserin (orcid)0000-0001-5518-6584 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 13(2021), 2 vom: 11. Jan. (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:13 year:2021 number:2 day:11 month:01 https://dx.doi.org/10.15252/emmm.202012632 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 13 2021 2 11 01 |
| spelling |
10.15252/emmm.202012632 doi (DE-627)SPR058031278 (SPR)emmm.202012632-e DE-627 ger DE-627 rakwb eng Bae, Mihyun verfasserin aut SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction. Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function. Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. glycine transporter (dpeaa)DE-He213 neuropsychiatric disorders (dpeaa)DE-He213 NMDA receptor (dpeaa)DE-He213 PTEN (dpeaa)DE-He213 Slc6a20 (dpeaa)DE-He213 Roh, Junyeop Daniel verfasserin aut Kim, Youjoung verfasserin aut Kim, Seong Soon verfasserin aut Han, Hye Min verfasserin aut Yang, Esther verfasserin aut Kang, Hyojin verfasserin aut Lee, Suho verfasserin aut Kim, Jin Yong verfasserin aut Kang, Ryeonghwa verfasserin aut Jung, Hwajin verfasserin aut Yoo, Taesun verfasserin aut Kim, Hyosang verfasserin aut Kim, Doyoun verfasserin (orcid)0000-0002-6036-8996 aut Oh, Heejeong verfasserin aut Han, Sungwook verfasserin aut Kim, Dayeon verfasserin aut Han, Jinju verfasserin (orcid)0000-0003-1844-2301 aut Bae, Yong Chul verfasserin (orcid)0000-0002-7618-418X aut Kim, Hyun verfasserin (orcid)0000-0001-8235-7553 aut Ahn, Sunjoo verfasserin aut Chan, Andrew M verfasserin (orcid)0000-0001-9923-5464 aut Lee, Daeyoup verfasserin (orcid)0000-0003-2006-1823 aut Kim, Jin Woo verfasserin (orcid)0000-0003-0767-1918 aut Kim, Eunjoon verfasserin (orcid)0000-0001-5518-6584 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 13(2021), 2 vom: 11. Jan. (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:13 year:2021 number:2 day:11 month:01 https://dx.doi.org/10.15252/emmm.202012632 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 13 2021 2 11 01 |
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10.15252/emmm.202012632 doi (DE-627)SPR058031278 (SPR)emmm.202012632-e DE-627 ger DE-627 rakwb eng Bae, Mihyun verfasserin aut SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction. Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function. Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. glycine transporter (dpeaa)DE-He213 neuropsychiatric disorders (dpeaa)DE-He213 NMDA receptor (dpeaa)DE-He213 PTEN (dpeaa)DE-He213 Slc6a20 (dpeaa)DE-He213 Roh, Junyeop Daniel verfasserin aut Kim, Youjoung verfasserin aut Kim, Seong Soon verfasserin aut Han, Hye Min verfasserin aut Yang, Esther verfasserin aut Kang, Hyojin verfasserin aut Lee, Suho verfasserin aut Kim, Jin Yong verfasserin aut Kang, Ryeonghwa verfasserin aut Jung, Hwajin verfasserin aut Yoo, Taesun verfasserin aut Kim, Hyosang verfasserin aut Kim, Doyoun verfasserin (orcid)0000-0002-6036-8996 aut Oh, Heejeong verfasserin aut Han, Sungwook verfasserin aut Kim, Dayeon verfasserin aut Han, Jinju verfasserin (orcid)0000-0003-1844-2301 aut Bae, Yong Chul verfasserin (orcid)0000-0002-7618-418X aut Kim, Hyun verfasserin (orcid)0000-0001-8235-7553 aut Ahn, Sunjoo verfasserin aut Chan, Andrew M verfasserin (orcid)0000-0001-9923-5464 aut Lee, Daeyoup verfasserin (orcid)0000-0003-2006-1823 aut Kim, Jin Woo verfasserin (orcid)0000-0003-0767-1918 aut Kim, Eunjoon verfasserin (orcid)0000-0001-5518-6584 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 13(2021), 2 vom: 11. Jan. (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:13 year:2021 number:2 day:11 month:01 https://dx.doi.org/10.15252/emmm.202012632 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 13 2021 2 11 01 |
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10.15252/emmm.202012632 doi (DE-627)SPR058031278 (SPR)emmm.202012632-e DE-627 ger DE-627 rakwb eng Bae, Mihyun verfasserin aut SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction. Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function. Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. glycine transporter (dpeaa)DE-He213 neuropsychiatric disorders (dpeaa)DE-He213 NMDA receptor (dpeaa)DE-He213 PTEN (dpeaa)DE-He213 Slc6a20 (dpeaa)DE-He213 Roh, Junyeop Daniel verfasserin aut Kim, Youjoung verfasserin aut Kim, Seong Soon verfasserin aut Han, Hye Min verfasserin aut Yang, Esther verfasserin aut Kang, Hyojin verfasserin aut Lee, Suho verfasserin aut Kim, Jin Yong verfasserin aut Kang, Ryeonghwa verfasserin aut Jung, Hwajin verfasserin aut Yoo, Taesun verfasserin aut Kim, Hyosang verfasserin aut Kim, Doyoun verfasserin (orcid)0000-0002-6036-8996 aut Oh, Heejeong verfasserin aut Han, Sungwook verfasserin aut Kim, Dayeon verfasserin aut Han, Jinju verfasserin (orcid)0000-0003-1844-2301 aut Bae, Yong Chul verfasserin (orcid)0000-0002-7618-418X aut Kim, Hyun verfasserin (orcid)0000-0001-8235-7553 aut Ahn, Sunjoo verfasserin aut Chan, Andrew M verfasserin (orcid)0000-0001-9923-5464 aut Lee, Daeyoup verfasserin (orcid)0000-0003-2006-1823 aut Kim, Jin Woo verfasserin (orcid)0000-0003-0767-1918 aut Kim, Eunjoon verfasserin (orcid)0000-0001-5518-6584 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 13(2021), 2 vom: 11. Jan. (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:13 year:2021 number:2 day:11 month:01 https://dx.doi.org/10.15252/emmm.202012632 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 13 2021 2 11 01 |
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10.15252/emmm.202012632 doi (DE-627)SPR058031278 (SPR)emmm.202012632-e DE-627 ger DE-627 rakwb eng Bae, Mihyun verfasserin aut SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction. Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function. Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. glycine transporter (dpeaa)DE-He213 neuropsychiatric disorders (dpeaa)DE-He213 NMDA receptor (dpeaa)DE-He213 PTEN (dpeaa)DE-He213 Slc6a20 (dpeaa)DE-He213 Roh, Junyeop Daniel verfasserin aut Kim, Youjoung verfasserin aut Kim, Seong Soon verfasserin aut Han, Hye Min verfasserin aut Yang, Esther verfasserin aut Kang, Hyojin verfasserin aut Lee, Suho verfasserin aut Kim, Jin Yong verfasserin aut Kang, Ryeonghwa verfasserin aut Jung, Hwajin verfasserin aut Yoo, Taesun verfasserin aut Kim, Hyosang verfasserin aut Kim, Doyoun verfasserin (orcid)0000-0002-6036-8996 aut Oh, Heejeong verfasserin aut Han, Sungwook verfasserin aut Kim, Dayeon verfasserin aut Han, Jinju verfasserin (orcid)0000-0003-1844-2301 aut Bae, Yong Chul verfasserin (orcid)0000-0002-7618-418X aut Kim, Hyun verfasserin (orcid)0000-0001-8235-7553 aut Ahn, Sunjoo verfasserin aut Chan, Andrew M verfasserin (orcid)0000-0001-9923-5464 aut Lee, Daeyoup verfasserin (orcid)0000-0003-2006-1823 aut Kim, Jin Woo verfasserin (orcid)0000-0003-0767-1918 aut Kim, Eunjoon verfasserin (orcid)0000-0001-5518-6584 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 13(2021), 2 vom: 11. Jan. (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:13 year:2021 number:2 day:11 month:01 https://dx.doi.org/10.15252/emmm.202012632 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4315 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 13 2021 2 11 01 |
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Enthalten in EMBO Molecular Medicine 13(2021), 2 vom: 11. Jan. volume:13 year:2021 number:2 day:11 month:01 |
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Enthalten in EMBO Molecular Medicine 13(2021), 2 vom: 11. Jan. volume:13 year:2021 number:2 day:11 month:01 |
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glycine transporter neuropsychiatric disorders NMDA receptor PTEN Slc6a20 |
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Bae, Mihyun @@aut@@ Roh, Junyeop Daniel @@aut@@ Kim, Youjoung @@aut@@ Kim, Seong Soon @@aut@@ Han, Hye Min @@aut@@ Yang, Esther @@aut@@ Kang, Hyojin @@aut@@ Lee, Suho @@aut@@ Kim, Jin Yong @@aut@@ Kang, Ryeonghwa @@aut@@ Jung, Hwajin @@aut@@ Yoo, Taesun @@aut@@ Kim, Hyosang @@aut@@ Kim, Doyoun @@aut@@ Oh, Heejeong @@aut@@ Han, Sungwook @@aut@@ Kim, Dayeon @@aut@@ Han, Jinju @@aut@@ Bae, Yong Chul @@aut@@ Kim, Hyun @@aut@@ Ahn, Sunjoo @@aut@@ Chan, Andrew M @@aut@@ Lee, Daeyoup @@aut@@ Kim, Jin Woo @@aut@@ Kim, Eunjoon @@aut@@ |
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2021-01-11T00:00:00Z |
| hierarchy_top_id |
594772761 |
| id |
SPR058031278 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR058031278</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20241024065232.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">241024s2021 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.15252/emmm.202012632</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR058031278</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)emmm.202012632-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Bae, Mihyun</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2021</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. 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|
| author |
Bae, Mihyun |
| spellingShingle |
Bae, Mihyun misc glycine transporter misc neuropsychiatric disorders misc NMDA receptor misc PTEN misc Slc6a20 SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function |
| authorStr |
Bae, Mihyun |
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@@773@@(DE-627)594772761 |
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electronic Article |
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SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function glycine transporter (dpeaa)DE-He213 neuropsychiatric disorders (dpeaa)DE-He213 NMDA receptor (dpeaa)DE-He213 PTEN (dpeaa)DE-He213 Slc6a20 (dpeaa)DE-He213 |
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SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function |
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SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function |
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Bae, Mihyun Roh, Junyeop Daniel Kim, Youjoung Kim, Seong Soon Han, Hye Min Yang, Esther Kang, Hyojin Lee, Suho Kim, Jin Yong Kang, Ryeonghwa Jung, Hwajin Yoo, Taesun Kim, Hyosang Kim, Doyoun Oh, Heejeong Han, Sungwook Kim, Dayeon Han, Jinju Bae, Yong Chul Kim, Hyun Ahn, Sunjoo Chan, Andrew M Lee, Daeyoup Kim, Jin Woo Kim, Eunjoon |
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10.15252/emmm.202012632 |
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slc6a20 transporter: a novel regulator of brain glycine homeostasis and nmdar function |
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SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function |
| abstract |
Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction. Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function. Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. © The Author(s) 2021 |
| abstractGer |
Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction. Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function. Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. © The Author(s) 2021 |
| abstract_unstemmed |
Abstract Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co‐agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β‐catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide‐induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction. Synopsis This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. SLC6A20A transports both glycine and proline in mammalian cells.PTEN C‐terminal deletion enhances SLC6A20A expression, brain glycine levels, and NMDA receptor function in mice.SLC6A20A haploinsufficient mice display increased brain glycine levels and enhanced NMDA receptor function. Graphical Abstract This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia. © The Author(s) 2021 |
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