Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions
Endoplasmic reticulum/plasma membrane (ER/PM) junctions are a major site of cellular signal transduction including in epithelia; however, whether their lipid membrane environment affects junctional ion transporters function remains unclear. Here, we show that epithelial secretion is governed by phos...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2025
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| Sorozat: | EMBO JOURNAL
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| Tárgyszavak: | |
| doi: | 10.1038/s44318-025-00470-9 |
| mtmt: | 36169776 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/36903 |
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| 024 | 7 | |a 36169776 |2 mtmt | |
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| 100 | 1 | |a Sarkar Paramita | |
| 245 | 1 | 0 | |a Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions |h [elektronikus dokumentum] / |c Sarkar Paramita |
| 260 | |c 2025 | ||
| 490 | 0 | |a EMBO JOURNAL | |
| 520 | 3 | |a Endoplasmic reticulum/plasma membrane (ER/PM) junctions are a major site of cellular signal transduction including in epithelia; however, whether their lipid membrane environment affects junctional ion transporters function remains unclear. Here, we show that epithelial secretion is governed by phosphatidylserine (PtdSer) levels in ER/PM nanodomains, specified by the antagonistic action of the lipid transfer proteins E-Syt3 and ORP5, which transduce cAMP signals to the chloride channel CFTR and activate the sodium-bicarbonate cotransporter NBCe1-B by IRBIT. Lipid transfer by E-Syt3, along with restricted plasma membrane localization by the E-Syt3 C2C domain, are essential for E-Syt3 function, as removal of PtdSer from junctions by E-Syt3 dissociated the cAMP signaling pathway complex, preventing CFTR activation, and prevented NBCe1-B activation by IRBIT. CFTR and NBCe1-B PtdSer sensor domains responded to PtdSer reduction by E-Syt3; which was reversed by exogenous PtdSer or by PtdSer supplied by ORP5. In mice, E-Syt3 depletion improved chloride flux and fluid secretion in salivary glands and isolated pancreatic ducts. These findings provide a framework for understanding the role of junctional lipids in the assembly of functional ion protein complexes and cellular communication at epithelial signaling hubs. | |
| 650 | 4 | |a Klinikai orvostan | |
| 700 | 0 | 1 | |a Lüscher Benjamin P |e aut |
| 700 | 0 | 1 | |a Ye Zengyou |e aut |
| 700 | 0 | 1 | |a Chung Woo Young |e aut |
| 700 | 0 | 1 | |a Abtahi Ava Movahed |e aut |
| 700 | 0 | 1 | |a Zheng Changyu |e aut |
| 700 | 0 | 1 | |a Lee Min Goo |e aut |
| 700 | 0 | 1 | |a Varga Árpád |e aut |
| 700 | 0 | 1 | |a Pallagi Petra |e aut |
| 700 | 0 | 1 | |a Maléth József |e aut |
| 700 | 0 | 1 | |a Ahuja Malini |e aut |
| 700 | 0 | 1 | |a Muallem Shmuel |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/36903/1/Sarkar2025.pdf |z Dokumentum-elérés |