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Here we showed that exocytosis of zymogen granules in acinar cells was driven by Ca\n                    <jats:sup>2+<\/jats:sup>\n                    directly released from acidic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    stores including secretory granules through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded by\n                    <jats:italic>Tmem63a<\/jats:italic>\n                    ) as an organellar Ca\n                    <jats:sup>2+<\/jats:sup>\n                    regulator protein integral to the membrane of secretory granules that controlled Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release via inhibition of TPC1 and TPC2 currents. Deletion of OCaR1 led to extensive Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release from NAADP-responsive granules under basal conditions as well as upon stimulation of GPCR receptors. 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Our findings showed OCaR1 as a gatekeeper of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release that endows NAADP-sensitive secretory granules with an autoregulatory mechanism preventing uncontrolled exocytosis and pancreatic tissue damage.\n                  <\/jats:p>","DOI":"10.1172\/jci169428","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T14:00:32Z","timestamp":1711893632000},"source":"Crossref","is-referenced-by-count":21,"title":["OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1275-3029","authenticated-orcid":true,"given":"Volodymyr","family":"Tsvilovskyy","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, Heidelberg University, Heidelberg, Germany."},{"name":"DZHK (German Centre for Cardiovascular Research), 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