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CAPS1 and CAPS2 Regulate Stability and Recruitment of Insulin Granules in Mouse Pancreatic beta Cells.

Author:
  • Dina Speidel
  • S Albert Salehi
  • Stefanie Obermueller
  • Ingmar Lundquist
  • Nils Brose
  • Erik Renström
  • Patrik Rorsman
Publishing year: 2008
Language: English
Pages: 57-67
Publication/Series: Cell Metabolism
Volume: 7
Issue: 1
Document type: Journal article
Publisher: Cell Press

Abstract english

CAPS1 and CAPS2 regulate dense-core vesicle release of transmitters and hormones in neuroendocrine cells, but their precise roles in the secretory process remain enigmatic. Here we show that CAPS2(-/-) and CAPS1(+/-);CAPS2(-/-) mice, despite having increased insulin sensitivity, are glucose intolerant and that this effect is attributable to a marked reduction of glucose-induced insulin secretion. This correlates with diminished Ca(2+)-dependent exocytosis, a reduction in the size of the morphologically docked pool, a decrease in the readily releasable pool of secretory vesicles, slowed granule priming, and suppression of second-phase (but not first-phase) insulin secretion. In beta cells of CAPS1(+/-);CAPS2(-/-) mice, the lowered insulin content and granule numbers were associated with an increase in lysosome numbers and lysosomal enzyme activity. We conclude that although CAPS proteins are not required for Ca(2+)-dependent exocytosis to proceed, they exert a modulatory effect on insulin granule priming, exocytosis, and stability.

Keywords

  • Cell and Molecular Biology

Other

Published
  • Islet patophysiology
  • Islet cell exocytosis
  • Islet cell physiology
  • ISSN: 1550-4131
Erik Renström
E-mail: erik [dot] renstrom [at] med [dot] lu [dot] se

Deputy head of department

Department of Clinical Sciences, Malmö

+46 40 39 11 57

+46 40 39 11 57

Principal investigator

Islet patophysiology

+46 40 39 11 57

+46 40 39 11 57

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