ArticleThe Journal of clinical investigation2024
OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- A TMEM63B variant with enhanced mechanosensitive channel activity and acquired lipid scramblase function.The Journal of general physiology · 2026Article
- Allosteric switching of CaThe EMBO journal · 2026Article
- TPC1-dependent control of endosomal pH and transferrin uptake determines cellular iron status.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.Traffic (Copenhagen, Denmark) · 2026Review
- Review
- From plasma membrane to lysosomes: expanding roles of TMEM63/OSCA channels in mechanosensation and intracellular signaling.Frontiers in pharmacology · 2026Review
- Pancreatic acinar cell signalling and function exhibit an absolute requirement for activation of GαThe Journal of physiology · 2025Article
- TMEM63A, associated with hypomyelinating leukodystrophies, is an evolutionarily conserved regulator of myelination.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cation Channel TMEM63A Autonomously Facilitates Oligodendrocyte Differentiation at an Early Stage.Neuroscience bulletin · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Two-pore channel regulators - Who is in control?Frontiers in physiology · 2024Review
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Authors and funding
40 authors at 13 institutions in 4 countries.
Funding
Abstract
Regulated exocytosis is initiated by increased Ca2+ concentrations in close spatial proximity to secretory granules, which is effectively prevented when the cell is at rest. Here we showed that exocytosis of zymogen granules in acinar cells was driven by Ca2+ directly released from acidic Ca2+ stores including secretory granules through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded by Tmem63a) as an organellar Ca2+ regulator protein integral to the membrane of secretory granules that controlled Ca2+ release via inhibition of TPC1 and TPC2 currents. Deletion of OCaR1 led to extensive Ca2+ release from NAADP-responsive granules under basal conditions as well as upon stimulation of GPCR receptors. Moreover, OCaR1 deletion exacerbated the disease phenotype in murine models of severe and chronic pancreatitis. Our findings showed OCaR1 as a gatekeeper of Ca2+ release that endows NAADP-sensitive secretory granules with an autoregulatory mechanism preventing uncontrolled exocytosis and pancreatic tissue damage.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.