CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway
Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan s...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Montoliu-Gaya, Laia [verfasserIn] Tietze, Daniel [verfasserIn] Kaminski, Debora [verfasserIn] Mirgorodskaya, Ekaterina [verfasserIn] Tietze, Alesia A [verfasserIn] Sterky, Fredrik H [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 Reports - Nature Publishing Group UK, 2023, 22(2021), 4 vom: 15. Feb. |
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| Übergeordnetes Werk: |
volume:22 ; year:2021 ; number:4 ; day:15 ; month:02 |
| Links: |
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| DOI / URN: |
10.15252/embr.202051349 |
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| Katalog-ID: |
SPR058026789 |
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| 245 | 1 | 0 | |a CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway |
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| 520 | |a Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations. | ||
| 520 | |a Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue. | ||
| 520 | |a Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin. | ||
| 650 | 4 | |a CA10 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a carbonic anhydrase-related protein |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a heparan sulfate |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a neurexin |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a synapse |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Tietze, Daniel |e verfasserin |0 (orcid)0000-0002-9251-1902 |4 aut | |
| 700 | 1 | |a Kaminski, Debora |e verfasserin |4 aut | |
| 700 | 1 | |a Mirgorodskaya, Ekaterina |e verfasserin |4 aut | |
| 700 | 1 | |a Tietze, Alesia A |e verfasserin |4 aut | |
| 700 | 1 | |a Sterky, Fredrik H |e verfasserin |0 (orcid)0000-0001-8881-0523 |4 aut | |
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10.15252/embr.202051349 doi (DE-627)SPR058026789 (SPR)embr.202051349-e DE-627 ger DE-627 rakwb eng Montoliu-Gaya, Laia verfasserin (orcid)0000-0001-7684-6318 aut CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations. Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue. Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin. CA10 (dpeaa)DE-He213 carbonic anhydrase-related protein (dpeaa)DE-He213 heparan sulfate (dpeaa)DE-He213 neurexin (dpeaa)DE-He213 synapse (dpeaa)DE-He213 Tietze, Daniel verfasserin (orcid)0000-0002-9251-1902 aut Kaminski, Debora verfasserin aut Mirgorodskaya, Ekaterina verfasserin aut Tietze, Alesia A verfasserin aut Sterky, Fredrik H verfasserin (orcid)0000-0001-8881-0523 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 4 vom: 15. Feb. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:4 day:15 month:02 https://dx.doi.org/10.15252/embr.202051349 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 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_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 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_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 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_2113 GBV_ILN_2118 GBV_ILN_2119 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_2472 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_4318 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 22 2021 4 15 02 |
| spelling |
10.15252/embr.202051349 doi (DE-627)SPR058026789 (SPR)embr.202051349-e DE-627 ger DE-627 rakwb eng Montoliu-Gaya, Laia verfasserin (orcid)0000-0001-7684-6318 aut CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations. Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue. Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin. CA10 (dpeaa)DE-He213 carbonic anhydrase-related protein (dpeaa)DE-He213 heparan sulfate (dpeaa)DE-He213 neurexin (dpeaa)DE-He213 synapse (dpeaa)DE-He213 Tietze, Daniel verfasserin (orcid)0000-0002-9251-1902 aut Kaminski, Debora verfasserin aut Mirgorodskaya, Ekaterina verfasserin aut Tietze, Alesia A verfasserin aut Sterky, Fredrik H verfasserin (orcid)0000-0001-8881-0523 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 4 vom: 15. Feb. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:4 day:15 month:02 https://dx.doi.org/10.15252/embr.202051349 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 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_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 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_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 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_2113 GBV_ILN_2118 GBV_ILN_2119 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_2472 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_4318 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 22 2021 4 15 02 |
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10.15252/embr.202051349 doi (DE-627)SPR058026789 (SPR)embr.202051349-e DE-627 ger DE-627 rakwb eng Montoliu-Gaya, Laia verfasserin (orcid)0000-0001-7684-6318 aut CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations. Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue. Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin. CA10 (dpeaa)DE-He213 carbonic anhydrase-related protein (dpeaa)DE-He213 heparan sulfate (dpeaa)DE-He213 neurexin (dpeaa)DE-He213 synapse (dpeaa)DE-He213 Tietze, Daniel verfasserin (orcid)0000-0002-9251-1902 aut Kaminski, Debora verfasserin aut Mirgorodskaya, Ekaterina verfasserin aut Tietze, Alesia A verfasserin aut Sterky, Fredrik H verfasserin (orcid)0000-0001-8881-0523 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 4 vom: 15. Feb. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:4 day:15 month:02 https://dx.doi.org/10.15252/embr.202051349 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 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_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 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_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 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_2113 GBV_ILN_2118 GBV_ILN_2119 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_2472 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_4318 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 22 2021 4 15 02 |
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10.15252/embr.202051349 doi (DE-627)SPR058026789 (SPR)embr.202051349-e DE-627 ger DE-627 rakwb eng Montoliu-Gaya, Laia verfasserin (orcid)0000-0001-7684-6318 aut CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations. Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue. Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin. CA10 (dpeaa)DE-He213 carbonic anhydrase-related protein (dpeaa)DE-He213 heparan sulfate (dpeaa)DE-He213 neurexin (dpeaa)DE-He213 synapse (dpeaa)DE-He213 Tietze, Daniel verfasserin (orcid)0000-0002-9251-1902 aut Kaminski, Debora verfasserin aut Mirgorodskaya, Ekaterina verfasserin aut Tietze, Alesia A verfasserin aut Sterky, Fredrik H verfasserin (orcid)0000-0001-8881-0523 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 4 vom: 15. Feb. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:4 day:15 month:02 https://dx.doi.org/10.15252/embr.202051349 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 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_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 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_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 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_2113 GBV_ILN_2118 GBV_ILN_2119 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_2472 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_4318 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 22 2021 4 15 02 |
| allfieldsSound |
10.15252/embr.202051349 doi (DE-627)SPR058026789 (SPR)embr.202051349-e DE-627 ger DE-627 rakwb eng Montoliu-Gaya, Laia verfasserin (orcid)0000-0001-7684-6318 aut CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations. Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue. Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin. CA10 (dpeaa)DE-He213 carbonic anhydrase-related protein (dpeaa)DE-He213 heparan sulfate (dpeaa)DE-He213 neurexin (dpeaa)DE-He213 synapse (dpeaa)DE-He213 Tietze, Daniel verfasserin (orcid)0000-0002-9251-1902 aut Kaminski, Debora verfasserin aut Mirgorodskaya, Ekaterina verfasserin aut Tietze, Alesia A verfasserin aut Sterky, Fredrik H verfasserin (orcid)0000-0001-8881-0523 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 22(2021), 4 vom: 15. Feb. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:22 year:2021 number:4 day:15 month:02 https://dx.doi.org/10.15252/embr.202051349 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 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_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 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_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 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_2113 GBV_ILN_2118 GBV_ILN_2119 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_2472 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_4318 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 22 2021 4 15 02 |
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Enthalten in EMBO Reports 22(2021), 4 vom: 15. Feb. volume:22 year:2021 number:4 day:15 month:02 |
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Enthalten in EMBO Reports 22(2021), 4 vom: 15. Feb. volume:22 year:2021 number:4 day:15 month:02 |
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CA10 carbonic anhydrase-related protein heparan sulfate neurexin synapse |
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Montoliu-Gaya, Laia @@aut@@ Tietze, Daniel @@aut@@ Kaminski, Debora @@aut@@ Mirgorodskaya, Ekaterina @@aut@@ Tietze, Alesia A @@aut@@ Sterky, Fredrik H @@aut@@ |
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Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CA10</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">carbonic anhydrase-related protein</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">heparan sulfate</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">neurexin</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">synapse</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tietze, Daniel</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-9251-1902</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kaminski, Debora</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mirgorodskaya, Ekaterina</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tietze, Alesia A</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sterky, Fredrik H</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0001-8881-0523</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">EMBO Reports</subfield><subfield code="d">Nature Publishing Group UK, 2023</subfield><subfield code="g">22(2021), 4 vom: 15. 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|
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Montoliu-Gaya, Laia |
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Montoliu-Gaya, Laia misc CA10 misc carbonic anhydrase-related protein misc heparan sulfate misc neurexin misc synapse CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway |
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CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway CA10 (dpeaa)DE-He213 carbonic anhydrase-related protein (dpeaa)DE-He213 heparan sulfate (dpeaa)DE-He213 neurexin (dpeaa)DE-He213 synapse (dpeaa)DE-He213 |
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misc CA10 misc carbonic anhydrase-related protein misc heparan sulfate misc neurexin misc synapse |
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CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway |
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CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway |
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Montoliu-Gaya, Laia |
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Montoliu-Gaya, Laia Tietze, Daniel Kaminski, Debora Mirgorodskaya, Ekaterina Tietze, Alesia A Sterky, Fredrik H |
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10.15252/embr.202051349 |
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ca10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway |
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CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway |
| abstract |
Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations. Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue. Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin. © The Author(s) 2021 |
| abstractGer |
Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations. Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue. Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin. © The Author(s) 2021 |
| abstract_unstemmed |
Abstract Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations. Synopsis CA10 binds to neurexins in the secretory pathway and blocks the addition of heparan sulfate to neurexins, which affects their ligand-binding properties. These findings illustrate a new mechanism to regulate site-specific glycosylations and a means to further diversify neurexin isoforms. Binding of the secreted protein CA10 to neurexins in the secretory pathway blocks the addition of heparan sulfate (HS) to neurexins.A direct interaction between CA10 and neurexin residues near the glycosylated serine prevents the primary step of HS biosynthesis: xylosylation of the serine residue. Graphical Abstract CA10 binds the presynaptic adhesion molecules neurexin in the secretory pathway and inhibits their modification with heparan sulfate, thereby modifying the ligand-binding properties of neurexin. © The Author(s) 2021 |
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CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway |
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Tietze, Daniel Kaminski, Debora Mirgorodskaya, Ekaterina Tietze, Alesia A Sterky, Fredrik H |
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| score |
7.402766 |