{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chung WY"],"funding":["HHS | NIH | National Institute of Dental and Craniofacial Research"],"pagination":["e2301410120"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10469337"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["120(35)"],"pubmed_abstract":["The membrane contact site ER/PM junctions are hubs for signaling pathways, including Ca<sup>2+</sup> signaling. Phosphatidylserine (PtdSer) mediates various physiological functions; however, junctional PtdSer composition and the role of PtdSer in Ca<sup>2+</sup> signaling and Ca<sup>2+</sup>-dependent gene regulation are not understood. Here, we show that STIM1-formed junctions are required for PI(4)P/PtdSer exchange by ORP5 and ORP8, which have reciprocal lipid exchange modes and function as a rheostat that sets the junctional PtdSer/PI(4)P ratio. Targeting the ORP5 and ORP8 and their lipid transfer ORD domains to PM subdomains revealed that ORP5 sets low and ORP8 high junctional PI(4)P/PtdSer ratio that controls STIM1-STIM1 and STIM1-Orai1 interaction and the activity of the SERCA pump t"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["PtdSer as a signaling lipid determined by privileged localization of ORP5 and ORP8 at ER/PM junctional foci to determine PM and ER PtdSer/PI(4)P ratio and cell function."],"pmcid":["PMC10469337"],"funding_grant_id":["DE000735-13"],"pubmed_authors":["Ohman HKE","Chung WY","McNally BA","Leibow SR","Movahed Abtahi A","Muallem S","Ahuja M"],"additional_accession":[]},"is_claimable":false,"name":"PtdSer as a signaling lipid determined by privileged localization of ORP5 and ORP8 at ER/PM junctional foci to determine PM and ER PtdSer/PI(4)P ratio and cell function.","description":"The membrane contact site ER/PM junctions are hubs for signaling pathways, including Ca<sup>2+</sup> signaling. Phosphatidylserine (PtdSer) mediates various physiological functions; however, junctional PtdSer composition and the role of PtdSer in Ca<sup>2+</sup> signaling and Ca<sup>2+</sup>-dependent gene regulation are not understood. Here, we show that STIM1-formed junctions are required for PI(4)P/PtdSer exchange by ORP5 and ORP8, which have reciprocal lipid exchange modes and function as a rheostat that sets the junctional PtdSer/PI(4)P ratio. Targeting the ORP5 and ORP8 and their lipid transfer ORD domains to PM subdomains revealed that ORP5 sets low and ORP8 high junctional PI(4)P/PtdSer ratio that controls STIM1-STIM1 and STIM1-Orai1 interaction and the activity of the SERCA pump t","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Aug","modification":"2025-04-26T08:06:25.368Z","creation":"2025-04-06T12:32:20.87Z"},"accession":"S-EPMC10469337","cross_references":{"pubmed":["37607230"],"doi":["10.1073/pnas.2301410120"]}}