{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:43:37Z","timestamp":1792406617825,"version":"4.4.0"},"reference-count":52,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["AI108636"],"award-info":[{"award-number":["AI108636"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"award":["AI108636"],"award-info":[{"award-number":["AI108636"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Department of Atomic Energy, Government of India","award":["RTI 4007"],"award-info":[{"award-number":["RTI 4007"]}],"id":[{"id":"https:\/\/ror.org\/036h6g940","id-type":"ROR","asserted-by":"crossref"}]},{"award":["RTI 4007"],"award-info":[{"award-number":["RTI 4007"]}],"id":[{"id":"https:\/\/ror.org\/036h6g940","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Indian Council of Medical Research","award":["EMDR\/SG\/11\/2025-01-02427"],"award-info":[{"award-number":["EMDR\/SG\/11\/2025-01-02427"]}],"id":[{"id":"https:\/\/ror.org\/0492wrx28","id-type":"ROR","asserted-by":"crossref"}]},{"award":["EMDR\/SG\/11\/2025-01-02427"],"award-info":[{"award-number":["EMDR\/SG\/11\/2025-01-02427"]}],"id":[{"id":"https:\/\/ror.org\/0492wrx28","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Mutations in Syntaxin11 (STX11), a Q-SNARE, result in a fatal immune disorder known as familial hemophagocytic lymphohistiocytosis 4 (FHLH4) in human patients. A key diagnostic feature of FHLH4 is defective T and natural killer cell cytotoxicity. Here, we show that STX11 directly binds and regulates Orai1, the pore-forming subunit of calcium release-activated calcium (CRAC) channels. CRAC channels enable store-operated calcium entry (SOCE) from the extracellular space and are crucial for granule exocytosis and nuclear factor of activated T cells (NFAT)-dependent gene expression in activated lymphocytes. STX11 depletion strongly inhibited SOCE, CRAC currents, NFAT activation, interleukin-2 gene expression, and degranulation in FHLH4 patient T lymphocytes and cell lines without affecting membrane trafficking. Remarkably, defects of cytolytic granule exocytosis, as well as interleukin-2 expression, could be reversed by ionomycin in patient T lymphocytes, and a constitutively active, H134S, mutant of Orai1 rescued calcium entry in STX11-depleted cells. Further analyses showed that STX11 \u2018primes\u2019 Orai1 for optimal on-site multimeric assembly, which was Stim independent but required for gating. Priming of ion channel pore subunits is, therefore, a primary function of specific SNAREs which may have preceded their role in membrane trafficking and vesicle fusion.<\/jats:p>","DOI":"10.7554\/elife.111335","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T14:30:19Z","timestamp":1779460219000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.111335","source":"Crossref","is-referenced-by-count":0,"title":["Syntaxin11 deficiency inhibits CRAC channel priming to suppress cytotoxicity and gene expression in T lymphocytes independent of membrane trafficking"],"prefix":"10.7554","volume":"15","author":[{"given":"Sritama","family":"Datta","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Abhikarsh","family":"Gupta","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Kunal M","family":"Jagetiya","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Resmi","family":"Bera","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Vikas R","family":"Tiwari","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Centre for Biological Sciences","place":["Bangalore, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Megumi","family":"Yamashita","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/000e0be47","id-type":"ROR","asserted-by":"publisher"}],"name":"Northwestern University, Feinberg School of Medicine","place":["Chicago, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Atharva R","family":"Yande","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Abdul","family":"Rishad","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Vishal","family":"Malik","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Sreejith","family":"Raran-Kurussi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Sandra","family":"Ammann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0245cg223","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Immunodeficiency, University of Freiburg","place":["Freiburg im Breisgau, Germany"]},{"id":[{"id":"https:\/\/ror.org\/0245cg223","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Transfusion Medicine and Gene Therapy, University of Freiburg","place":["Freiburg im Breisgau, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"}]},{"given":"Mohammad","family":"Shahrooei","sequence":"additional","affiliation":[{"name":"Dr. Shahrooei Lab","place":["Tehran, Iran"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"}]},{"given":"Kalyaneswar","family":"Mandal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Ramanathan","family":"Sowdhamini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Centre for Biological Sciences","place":["Bangalore, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0781-4480","authenticated-orcid":true,"given":"Murali","family":"Prakriya","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/000e0be47","id-type":"ROR","asserted-by":"publisher"}],"name":"Northwestern University, Feinberg School of Medicine","place":["Chicago, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5491-7709","authenticated-orcid":true,"given":"Adish","family":"Dani","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-8853","authenticated-orcid":true,"given":"Monika","family":"Vig","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ht1xw27","id-type":"ROR","asserted-by":"publisher"}],"name":"Tata Institute of Fundamental Research","place":["Hyderabad, India"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2022.102616","type":"journal-article","article-title":"Discovery of novel gating checkpoints in the Orai1 calcium channel by systematic analysis of constitutively active mutants of its paralogs and orthologs","volume":"105","author":"Augustynek","year":"2022","journal-title":"Cell Calcium"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nrmicro1131","type":"journal-article","article-title":"Opinion: cell entry machines: a common theme in nature?","volume":"3","author":"Barocchi","year":"2005","journal-title":"Nature Reviews. Microbiology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1182\/blood-2007-02-074468","type":"journal-article","article-title":"Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients","volume":"110","author":"Bryceson","year":"2007","journal-title":"Blood"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/j.bbamcr.2017.05.018","type":"journal-article","article-title":"ER-plasma membrane junctions: Why and how do we study them?","volume":"1864","author":"Chang","year":"2017","journal-title":"Biochimica et Biophysica Acta. Molecular Cell Research"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1182\/blood-2017-11-814244","type":"journal-article","article-title":"Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis","volume":"132","author":"Chinn","year":"2018","journal-title":"Blood"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.cell.2007.11.028","type":"journal-article","article-title":"Calcium signaling","volume":"131","author":"Clapham","year":"2007","journal-title":"Cell"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"12477","DOI":"10.1073\/pnas.192203899","type":"journal-article","article-title":"CFTR chloride channels are regulated by a SNAP-23\/syntaxin 1A complex","volume":"99","author":"Cormet-Boyaka","year":"2002","journal-title":"PNAS"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"46896","DOI":"10.1074\/jbc.M407227200","type":"journal-article","article-title":"Conservation of the biochemical properties of IncA from Chlamydia trachomatis and Chlamydia caviae: oligomerization of IncA mediates interaction between facing membranes","volume":"279","author":"Delevoye","year":"2004","journal-title":"The Journal of Biological Chemistry"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1002\/eji.201142343","type":"journal-article","article-title":"Syntaxin 11 is required for NK and CD8","volume":"43","author":"D\u2019Orlando","year":"2013","journal-title":"European Journal of Immunology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"2697","DOI":"10.1073\/pnas.0611318104","type":"journal-article","article-title":"Munc18-1 binds directly to the neuronal SNARE complex","volume":"104","author":"Dulubova","year":"2007","journal-title":"PNAS"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nature04702","type":"journal-article","article-title":"A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function","volume":"441","author":"Feske","year":"2006","journal-title":"Nature"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"E4482","DOI":"10.1073\/pnas.1313474110","type":"journal-article","article-title":"Syntaxin binding mechanism and disease-causing mutations in Munc18-2","volume":"110","author":"Hackmann","year":"2013","journal-title":"PNAS"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098900","type":"journal-article","article-title":"Analysis of familial hemophagocytic lymphohistiocytosis type 4 (FHL-4) mutant proteins reveals that S-acylation is required for the function of syntaxin 11 in natural killer cells","volume":"9","author":"Hellewell","year":"2014","journal-title":"PLOS ONE"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36758","type":"journal-article","article-title":"Structures reveal opening of the store-operated calcium channel Orai","volume":"7","author":"Hou","year":"2018","journal-title":"eLife"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/nrm2002","type":"journal-article","article-title":"SNAREs--engines for membrane fusion","volume":"7","author":"Jahn","year":"2006","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.ceca.2005.01.017","type":"journal-article","article-title":"Masters or slaves? Vesicle release machinery and the regulation of presynaptic calcium channels","volume":"37","author":"Jarvis","year":"2005","journal-title":"Cell Calcium"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00448","type":"journal-article","article-title":"Graded defects in cytotoxicity determine severity of hemophagocytic lymphohistiocytosis in humans and mice","volume":"4","author":"Jessen","year":"2013","journal-title":"Frontiers in Immunology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.1093\/emboj\/20.9.2202","type":"journal-article","article-title":"SNAREs are concentrated in cholesterol-dependent clusters that define docking and fusion sites for exocytosis","volume":"20","author":"Lang","year":"2001","journal-title":"The EMBO Journal"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-68476-3","type":"journal-article","article-title":"Munc18-1 induces conformational changes of syntaxin-1 in multiple intermediates for SNARE assembly","volume":"10","author":"Lee","year":"2020","journal-title":"Scientific Reports"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/cr.2010.131","type":"journal-article","article-title":"Graded activation of CRAC channel by binding of different numbers of STIM1 to Orai1 subunits","volume":"21","author":"Li","year":"2011","journal-title":"Cell Research"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1091\/mbc.E16-03-0163","type":"journal-article","article-title":"\u03b1-SNAP regulates dynamic, on-site assembly and calcium selectivity of Orai1 channels","volume":"27","author":"Li","year":"2016","journal-title":"Molecular Biology of the Cell"},{"key":"bib22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150723","type":"journal-article","article-title":"Activated human Orai1 channel in lipid biolayer may exist as a pentamer","volume":"733","author":"Lu","year":"2024","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1002\/pbc.22676","type":"journal-article","article-title":"Unusual functional manifestations of a novel STX11 frameshift mutation in two infants with familial hemophagocytic lymphohistiocytosis type 4 (FHL4)","volume":"56","author":"Macartney","year":"2011","journal-title":"Pediatric Blood & Cancer"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1002\/pbc.22499","type":"journal-article","article-title":"STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America","volume":"55","author":"Marsh","year":"2010","journal-title":"Pediatric Blood & Cancer"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"3324","DOI":"10.1073\/pnas.1013285108","type":"journal-article","article-title":"ORAI1-mediated calcium influx is required for human cytotoxic lymphocyte degranulation and target cell lysis","volume":"108","author":"Maul-Pavicic","year":"2011","journal-title":"PNAS"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1091\/mbc.1.4.369","type":"journal-article","article-title":"Human transferrin receptor internalization is partially dependent upon an aromatic amino acid on the cytoplasmic domain","volume":"1","author":"McGraw","year":"1990","journal-title":"Cell Regulation"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/nature10752","type":"journal-article","article-title":"Gated regulation of CRAC channel ion selectivity by STIM1","volume":"482","author":"McNally","year":"2012","journal-title":"Nature"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"24979","DOI":"10.1074\/jbc.M604589200","type":"journal-article","article-title":"Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1","volume":"281","author":"Mercer","year":"2006","journal-title":"The Journal of Biological Chemistry"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00802","type":"journal-article","article-title":"An essential and NSF independent role for \u03b1-SNAP in store-operated calcium entry","volume":"2","author":"Miao","year":"2013","journal-title":"eLife"},{"key":"bib30","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25155","type":"journal-article","article-title":"Na+ influx via Orai1 inhibits intracellular ATP-induced mTORC2 signaling to disrupt CD4 T cell gene expression and differentiation","volume":"6","author":"Miao","year":"2017","journal-title":"eLife"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00515","type":"journal-article","article-title":"An N-Terminal missense mutation in STX11 causative of FHL4 Abrogates Syntaxin-11 Binding to Munc18-2","volume":"4","author":"M\u00fcller","year":"2014","journal-title":"Frontiers in Immunology"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"2468","DOI":"10.1016\/j.cub.2020.04.060","type":"journal-article","article-title":"Prototypic SNARE proteins are encoded in the genomes of heimdallarchaeota, potentially bridging the gap between the prokaryotes and eukaryotes","volume":"30","author":"Neveu","year":"2020","journal-title":"Current Biology"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.cell.2009.02.014","type":"journal-article","article-title":"STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1","volume":"136","author":"Park","year":"2009","journal-title":"Cell"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007375","type":"journal-article","article-title":"Intracellular bacteria encode inhibitory SNARE-like proteins","volume":"4","author":"Paumet","year":"2009","journal-title":"PLOS ONE"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/ncb1435","type":"journal-article","article-title":"Amplification of CRAC current by STIM1 and CRACM1 (Orai1)","volume":"8","author":"Peinelt","year":"2006","journal-title":"Nature Cell Biology"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1085\/jgp.200609588","type":"journal-article","article-title":"Regulation of CRAC channel activity by recruitment of silent channels to a high open-probability gating mode","volume":"128","author":"Prakriya","year":"2006","journal-title":"The Journal of General Physiology"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1152\/physrev.00020.2014","type":"journal-article","article-title":"Store-operated calcium channels","volume":"95","author":"Prakriya","year":"2015","journal-title":"Physiological Reviews"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0258670","type":"journal-article","article-title":"High affinity associations with \u03b1-SNAP enable calcium entry via Orai1 channels","volume":"16","author":"Ramanagoudr-Bhojappa","year":"2021","journal-title":"PLOS ONE"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"20661","DOI":"10.1074\/jbc.C600126200","type":"journal-article","article-title":"Orai1 and STIM reconstitute store-operated calcium channel function","volume":"281","author":"Soboloff","year":"2006","journal-title":"The Journal of Biological Chemistry"},{"key":"bib40","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3963","type":"journal-article","article-title":"STIM1\/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry","volume":"4","author":"Stathopulos","year":"2013","journal-title":"Nature Communications"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.1091\/mbc.E16-03-0184","type":"journal-article","article-title":"Regulation of Ca2+ channels by SNAP-25 via recruitment of syntaxin-1 from plasma membrane clusters","volume":"27","author":"Toft-Bertelsen","year":"2016","journal-title":"Molecular Biology of the Cell"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/nature10545","type":"journal-article","article-title":"Membrane protein sequestering by ionic protein-lipid interactions","volume":"479","author":"van den Bogaart","year":"2011","journal-title":"Nature"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1016\/j.cub.2006.08.085","type":"journal-article","article-title":"CRACM1 multimers form the ion-selective pore of the CRAC channel","volume":"16","author":"Vig","year":"2006","journal-title":"Current Biology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1126\/science.1127883","type":"journal-article","article-title":"CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry","volume":"312","author":"Vig","year":"2006","journal-title":"Science"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.ceca.2007.03.008","type":"journal-article","article-title":"The long and arduous road to CRAC","volume":"42","author":"Vig","year":"2007","journal-title":"Cell Calcium"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/ni1550","type":"journal-article","article-title":"Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels","volume":"9","author":"Vig","year":"2008","journal-title":"Nature Immunology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/ni.f.220","type":"journal-article","article-title":"Calcium signaling in immune cells","volume":"10","author":"Vig","year":"2009","journal-title":"Nature Immunology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"R397","DOI":"10.1016\/j.cub.2018.01.005","type":"journal-article","article-title":"SNARE complex assembly and disassembly","volume":"28","author":"Yoon","year":"2018","journal-title":"Current Biology"},{"key":"bib49","type":"book-chapter","article-title":"Familial hemophagocytic lymphohistiocytosis","volume-title":"GeneReviews","author":"Zhang","year":"1993"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"9357","DOI":"10.1073\/pnas.0603161103","type":"journal-article","article-title":"Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity","volume":"103","author":"Zhang","year":"2006","journal-title":"PNAS"},{"key":"bib51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0348440","type":"journal-article","article-title":"Structural dynamics of the human Orai1 channel revealed by cryo-electron microscopy","volume":"21","author":"Zhang","year":"2026","journal-title":"PLOS ONE"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13725","type":"journal-article","article-title":"The STIM1-binding site nexus remotely controls Orai1 channel gating","volume":"7","author":"Zhou","year":"2016","journal-title":"Nature Communications"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/111335\/elife-111335-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/111335\/elife-111335-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/111335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:00:42Z","timestamp":1792404042000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/111335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,19]]},"references-count":52,"alternative-id":["10.7554\/eLife.111335"],"URL":"https:\/\/doi.org\/10.7554\/elife.111335","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.10.25.620144","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.111335.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.111335.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.111335.2","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,19]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP111335"}}