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 (Tom) Shearer, Mark D. Turner

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

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
Volume19
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Exocytosis
Synaptosomal-Associated Protein 25
Protein Isoforms
Proteolysis
Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
Vesicle-Associated Membrane Protein 2
Syntaxin 1
Insulin
Secretory Vesicles
Protease Inhibitors
Type 2 Diabetes Mellitus
calpain 10
Genome
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Marshall, C., Hitman, G. A., Partridge, C. J., Clark, A., Ma, H., Shearer, T. T., & Turner, M. D. (2005). Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic β-cells. Molecular Endocrinology, 19(1), 213-224. https://doi.org/10.1210/me.2004-0064

Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic β-cells. / Marshall, Catriona; Hitman, Graham A.; Partridge, Christopher J.; Clark, Anne; Ma, Hong; Shearer, Thomas (Tom); Turner, Mark D.

In: Molecular Endocrinology, Vol. 19, No. 1, 01.2005, p. 213-224.

Research output: Contribution to journalArticle

Marshall, C, Hitman, GA, Partridge, CJ, Clark, A, Ma, H, Shearer, TT & Turner, MD 2005, 'Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic β-cells', Molecular Endocrinology, vol. 19, no. 1, pp. 213-224. https://doi.org/10.1210/me.2004-0064
Marshall, Catriona ; Hitman, Graham A. ; Partridge, Christopher J. ; Clark, Anne ; Ma, Hong ; Shearer, Thomas (Tom) ; Turner, Mark D. / Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic β-cells. In: Molecular Endocrinology. 2005 ; Vol. 19, No. 1. pp. 213-224.
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