Syntaxin 4 and Synip (syntaxin 4 interacting protein) regulate insulin secretion in the pancreatic β HC-9 cell

Tsugumichi Saito, Shuichi Okada, Eijiro Yamada, Kihachi Ohshima, Hiroyuki Shimizu, Kenju Shimomura, Minoru Sato, Jeffrey E. Pessin, Masatomo Mori

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Although syntaxin 1 is generally thought to function as the primary target-N-ethylmaleimide-sensitive factor attachment protein receptor required for pancreatic β cell insulin secretion, we have observed that overexpression of a dominant-interfering syntaxin 4 mutant (syntaxin 4/ΔTM) attenuated glucose-stimulated insulin secretion in βHC-9 cells. Furthermore, these cells express the selective syntaxin 4-binding protein Synip (syntaxin 4 interacting protein), and Synip was specifically co-immunoprecipitated with syntaxin 4 but not syntaxin 1. Overexpression of the full-length Synip protein (Synip/wild type) inhibited VAMP2 association with syntaxin 4 and decreased glucose-stimulated insulin secretion. This did not occur with a Synip mutant (Synip/ΔEF) that was incapable of binding syntaxin 4. Consistent with a functional role of syntaxin 4 in this process, expression of syntaxin 4/ΔTM also inhibited glucose-stimulated insulin secretion. Furthermore, analysis of first and second phase insulin secretion demonstrated that syntaxin 4/ΔTM mainly suppressed the second phase of insulin secretion. In contrast, overexpression of Synip resulted in an inhibition of both the first and second phase of glucose-stimulated insulin secretion. These data demonstrate that syntaxin 4 plays a functional role on insulin release and granule fusion in β cells and that this process is regulated by the syntaxin 4-specific binding protein Synip.

Original languageEnglish (US)
Pages (from-to)36718-36725
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number38
DOIs
StatePublished - Sep 19 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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