Adenovirus-mediated silencing of Synaptotagmin 9 inhibits Ca 2+-dependent insulin secretion in islets

Mariella Iezzi, Lena Eliasson, Mitsunori Fukuda, Claes B. Wollheim

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Synaptotagmins (Syts) are involved in Ca2+-dependent insulin release. However, which Syt isoform is functional in primary β-cells remains unknown. We demonstrate by electron microscopy of pancreatic islets, the association of Syt 9 with insulin granules. Silencing of Syt 9 by RNA interference adenovirus in islet cells had no effect on the expression of Syt 5, Syt 7 and Syt 3 isoforms. The latter was localized at the plasma membrane of pancreatic polypeptide cells. Insulin release in response to glucose or tolbutamide was strongly inhibited in Syt 9 deficient islets, whereas exocytosis potentiated by raising cAMP levels, was unaltered. Thus, Syt 9 may act as Ca2+ sensor for β-cell secretion.

Original languageEnglish
Pages (from-to)5241-5246
Number of pages6
JournalFEBS Letters
Volume579
Issue number23
DOIs
Publication statusPublished - 2005 Sep 26
Externally publishedYes

Keywords

  • Electron microscopy
  • Insulin exocytosis
  • Pancreatic islets
  • RNA interference
  • β-cell

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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