Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic β-cells

Catriona Marshall, Graham A. Hitman, Christopher J. Partridge, Anne Clark, Hong Ma, Thomas R. Shearer, Mark D. Turner

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Calpain-10 (CAPN10) is the first type 2 diabetes susceptibility gene to be identified through a genome scan, with polymorphisms being associated with altered CAPN10 expression. Functional data have been hitherto elusive, but we report here a corresponding increase between CAPN10 expression level and regulated insulin secretion. Pancreatic β-cell secretory granule exocytosis is mediated by the soluble N-ethylmaleimide-sensitive fusion protein attachment receptor protein complex of synaptosomal-associated protein of 25 kDa (SNAP-25), syntaxin 1, and vesicle-associated membrane protein 2. We report, for the first time, direct binding of a calpain-10 isoform with members of this complex. Furthermore, SNAP-25 undergoes a Ca2+-dependent partial proteolysis during exocytosis, with calpain protease inhibitor similarly suppressing both insulin secretion and SNAP-25 proteolysis. Based upon these findings, we postulate that an isoform of calpain-10 is a Ca2+-sensor that functions to trigger exocytosis in pancreatic β-cells.

Original languageEnglish (US)
Pages (from-to)213-224
Number of pages12
JournalMolecular Endocrinology
Issue number1
StatePublished - Jan 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology


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