Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions

ABSTRACT: 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 antagonistic action of the lipid transfer proteins E-Syt3 and ORP5, which transduce cAMP signals to 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

SUBMITTER: Paramita Sarkar 

PROVIDER: S-SCDT-10_1038-S44318-025-00470-9 | biostudies-other |

REPOSITORIES: biostudies-other