{"doi":"10.1073/pnas.0611692104","title":"Orai proteins interact with TRPC channels and confer responsiveness to store depletion","abstract":"<jats:p>\n                    The TRPC (C-type transient receptor potential) class of ion channels has been hypothesized to participate in store-operated Ca\n                    <jats:sup>2+</jats:sup>\n                    entry (SOCE). Recently, however, STIM1 and Orai1 proteins have been proposed to form SOCE channels. Whether TRPCs participate in SOCE that is dependent on or regulated by Orai has not been explored. Here we show that Orai1 physically interacts with the N and C termini of TRPC3 and TRPC6, and that in cells overexpressing either TRPC3 or TRPC6 in a store-depletion insensitive manner, these TRPCs become sensitive to store depletion upon expression of an exogenous Orai. Thus, Orai-1, -2, and -3 enhanced thapsigargin-induced calcium entry by 50–150% in cells stably overexpressing either TRPC3 or TRPC6. Orai1 expression had no significant effect on endogenous, thapsigargin-induced calcium entry in wild-type cells (HEK-293, COS1), in HEK cells expressing a thapsigargin-sensitive variant of TRPC3 (TRPC3a), or in HEK cells overexpressing another membrane protein, V1aR. Single-channel cation currents present in membrane patches of TRPC3-overexpressing cells were suppressed by expression of Orai1. We propose that Orai proteins by interacting with TRPCs act as regulatory subunits that confer STIM1-mediated store depletion sensitivity to these channels.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2007,"id":24790,"datarank":10.571975211705674,"base_score":5.6937321388027,"endowment":5.6937321388027,"self_citation_contribution":0.8540598208204051,"citation_network_contribution":9.717915390885269,"self_endowment_contribution":0.8540598208204051,"citer_contribution":9.717915390885269,"corpus_percentile":null,"corpus_rank":null,"citation_count":296,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":147725,"name":"Christian Erxleben","orcid":null,"position":1,"is_corresponding":false},{"id":147726,"name":"Eda Yildirim","orcid":null,"position":2,"is_corresponding":false},{"id":147727,"name":"Joel Abramowitz","orcid":null,"position":3,"is_corresponding":false},{"id":147728,"name":"David L. Armstrong","orcid":null,"position":4,"is_corresponding":false},{"id":110422,"name":"Lutz Birnbaumer","orcid":"0000-0002-0775-8661","position":5,"is_corresponding":false},{"id":147724,"name":"Yanhong Liao","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.6937321388027,"endowment":5.6937321388027,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17360584","pmcid":"PMC1838661","openalex_id":"https://openalex.org/W2167479299","authors":[],"funders":[{"funder_name":"Intramural NIH HHS","grant_id":"","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"","title":null}],"total_grants":2,"fwci":14.2231,"citation_percentile":0.99555323,"influential_citations":23,"citation_trend":[{"year":2012,"count":27},{"year":2013,"count":14},{"year":2014,"count":14},{"year":2015,"count":12},{"year":2016,"count":14},{"year":2017,"count":13},{"year":2018,"count":5},{"year":2019,"count":5},{"year":2020,"count":10},{"year":2021,"count":7},{"year":2022,"count":10},{"year":2023,"count":8},{"year":2024,"count":2},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1838661","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc1838661?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1838661","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0611692104","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0611692104","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17360584","host_type":"repository"}],"fields_of_study":["Ion Channels and Receptors","Phytochemicals and Antioxidant Activities","Neurobiology and Insect Physiology Research","Biology","Medicine","Animals","COS Cells","Calcium","Calcium Channels","Cell Line","Chlorocebus aethiops","Electrophysiology","Humans","Models, Biological","Models, Genetic","ORAI1 Protein","Protein Binding","Protein Structure, Tertiary","TRPC Cation Channels","TRPC6 Cation Channel"],"mesh_terms":["ORAI1 Protein","TRPC6 Cation Channel","Animals","Calcium","Cell Line","Chlorocebus aethiops","Electrophysiology","Humans","Models, Biological","Models, Genetic","Protein Binding","Calcium Channels","Protein Structure, Tertiary","COS Cells","TRPC Cation Channels"],"keywords":["TRPC3","TRPC","TRPC6","ORAI1","TRPC5","Thapsigargin","Transient receptor potential channel","STIM1","Cell biology","TRPC1","HEK 293 cells","Chemistry","Voltage-dependent calcium channel","Calcium signaling","Ion channel","Calcium","Biology","Receptor","Signal transduction","Intracellular","Biochemistry","Endoplasmic reticulum"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T23:14:45.982319Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}