Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis
Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogo...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Niu, Yang [verfasserIn] Pemberton, Joshua G [verfasserIn] Kim, Yeun Ju [verfasserIn] Balla, Tamas [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2024 |
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| Schlagwörter: |
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| Anmerkung: |
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 |
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| Übergeordnetes Werk: |
Enthalten in: The EMBO Journal - Nature Publishing Group UK, 2023, 43(2024), 16 vom: 25. Juni, Seite 3414-3449 |
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| Übergeordnetes Werk: |
volume:43 ; year:2024 ; number:16 ; day:25 ; month:06 ; pages:3414-3449 |
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| DOI / URN: |
10.1038/s44318-024-00151-z |
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| Katalog-ID: |
SPR056998244 |
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| 520 | |a Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. | ||
| 520 | |a Synopsis Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR).PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum.Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane.Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. | ||
| 520 | |a Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. | ||
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| 650 | 4 | |a Phosphatidylserine |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Phosphatidylcholine |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Pemberton, Joshua G |e verfasserin |0 (orcid)0000-0002-1492-1471 |4 aut | |
| 700 | 1 | |a Kim, Yeun Ju |e verfasserin |0 (orcid)0009-0007-0416-8205 |4 aut | |
| 700 | 1 | |a Balla, Tamas |e verfasserin |0 (orcid)0000-0002-9077-3335 |4 aut | |
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10.1038/s44318-024-00151-z doi (DE-627)SPR056998244 (SPR)s44318-024-00151-z-e DE-627 ger DE-627 rakwb eng Niu, Yang verfasserin (orcid)0009-0008-9445-6266 aut Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. Synopsis Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR).PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum.Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane.Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. CCTα (dpeaa)DE-He213 Lipin1α (dpeaa)DE-He213 Nuclear Membrane (dpeaa)DE-He213 Phosphatidylserine (dpeaa)DE-He213 Phosphatidylcholine (dpeaa)DE-He213 Pemberton, Joshua G verfasserin (orcid)0000-0002-1492-1471 aut Kim, Yeun Ju verfasserin (orcid)0009-0007-0416-8205 aut Balla, Tamas verfasserin (orcid)0000-0002-9077-3335 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 43(2024), 16 vom: 25. Juni, Seite 3414-3449 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:43 year:2024 number:16 day:25 month:06 pages:3414-3449 https://dx.doi.org/10.1038/s44318-024-00151-z 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2059 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2024 16 25 06 3414-3449 |
| spelling |
10.1038/s44318-024-00151-z doi (DE-627)SPR056998244 (SPR)s44318-024-00151-z-e DE-627 ger DE-627 rakwb eng Niu, Yang verfasserin (orcid)0009-0008-9445-6266 aut Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. Synopsis Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR).PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum.Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane.Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. CCTα (dpeaa)DE-He213 Lipin1α (dpeaa)DE-He213 Nuclear Membrane (dpeaa)DE-He213 Phosphatidylserine (dpeaa)DE-He213 Phosphatidylcholine (dpeaa)DE-He213 Pemberton, Joshua G verfasserin (orcid)0000-0002-1492-1471 aut Kim, Yeun Ju verfasserin (orcid)0009-0007-0416-8205 aut Balla, Tamas verfasserin (orcid)0000-0002-9077-3335 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 43(2024), 16 vom: 25. Juni, Seite 3414-3449 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:43 year:2024 number:16 day:25 month:06 pages:3414-3449 https://dx.doi.org/10.1038/s44318-024-00151-z 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2059 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2024 16 25 06 3414-3449 |
| allfields_unstemmed |
10.1038/s44318-024-00151-z doi (DE-627)SPR056998244 (SPR)s44318-024-00151-z-e DE-627 ger DE-627 rakwb eng Niu, Yang verfasserin (orcid)0009-0008-9445-6266 aut Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. Synopsis Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR).PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum.Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane.Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. CCTα (dpeaa)DE-He213 Lipin1α (dpeaa)DE-He213 Nuclear Membrane (dpeaa)DE-He213 Phosphatidylserine (dpeaa)DE-He213 Phosphatidylcholine (dpeaa)DE-He213 Pemberton, Joshua G verfasserin (orcid)0000-0002-1492-1471 aut Kim, Yeun Ju verfasserin (orcid)0009-0007-0416-8205 aut Balla, Tamas verfasserin (orcid)0000-0002-9077-3335 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 43(2024), 16 vom: 25. Juni, Seite 3414-3449 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:43 year:2024 number:16 day:25 month:06 pages:3414-3449 https://dx.doi.org/10.1038/s44318-024-00151-z 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2059 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2024 16 25 06 3414-3449 |
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10.1038/s44318-024-00151-z doi (DE-627)SPR056998244 (SPR)s44318-024-00151-z-e DE-627 ger DE-627 rakwb eng Niu, Yang verfasserin (orcid)0009-0008-9445-6266 aut Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. Synopsis Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR).PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum.Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane.Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. CCTα (dpeaa)DE-He213 Lipin1α (dpeaa)DE-He213 Nuclear Membrane (dpeaa)DE-He213 Phosphatidylserine (dpeaa)DE-He213 Phosphatidylcholine (dpeaa)DE-He213 Pemberton, Joshua G verfasserin (orcid)0000-0002-1492-1471 aut Kim, Yeun Ju verfasserin (orcid)0009-0007-0416-8205 aut Balla, Tamas verfasserin (orcid)0000-0002-9077-3335 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 43(2024), 16 vom: 25. Juni, Seite 3414-3449 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:43 year:2024 number:16 day:25 month:06 pages:3414-3449 https://dx.doi.org/10.1038/s44318-024-00151-z 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2059 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2024 16 25 06 3414-3449 |
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10.1038/s44318-024-00151-z doi (DE-627)SPR056998244 (SPR)s44318-024-00151-z-e DE-627 ger DE-627 rakwb eng Niu, Yang verfasserin (orcid)0009-0008-9445-6266 aut Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. Synopsis Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR).PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum.Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane.Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. CCTα (dpeaa)DE-He213 Lipin1α (dpeaa)DE-He213 Nuclear Membrane (dpeaa)DE-He213 Phosphatidylserine (dpeaa)DE-He213 Phosphatidylcholine (dpeaa)DE-He213 Pemberton, Joshua G verfasserin (orcid)0000-0002-1492-1471 aut Kim, Yeun Ju verfasserin (orcid)0009-0007-0416-8205 aut Balla, Tamas verfasserin (orcid)0000-0002-9077-3335 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 43(2024), 16 vom: 25. Juni, Seite 3414-3449 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:43 year:2024 number:16 day:25 month:06 pages:3414-3449 https://dx.doi.org/10.1038/s44318-024-00151-z 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2059 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 43 2024 16 25 06 3414-3449 |
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Niu, Yang misc CCTα misc Lipin1α misc Nuclear Membrane misc Phosphatidylserine misc Phosphatidylcholine Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis |
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Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis CCTα (dpeaa)DE-He213 Lipin1α (dpeaa)DE-He213 Nuclear Membrane (dpeaa)DE-He213 Phosphatidylserine (dpeaa)DE-He213 Phosphatidylcholine (dpeaa)DE-He213 |
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phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis |
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Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis |
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Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. Synopsis Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR).PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum.Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane.Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 |
| abstractGer |
Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. Synopsis Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR).PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum.Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane.Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 |
| abstract_unstemmed |
Abstract Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. Synopsis Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR).PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum.Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane.Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 |
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| score |
7.4017773 |