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 journalArticle

30 Citations (Scopus)

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

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Qa-SNARE Proteins
Insulin
Proteins
Syntaxin 1
Glucose
Carrier Proteins
N-Ethylmaleimide-Sensitive Proteins
Vesicle-Associated Membrane Protein 2

ASJC Scopus subject areas

  • Biochemistry

Cite this

Saito, T., Okada, S., Yamada, E., Ohshima, K., Shimizu, H., Shimomura, K., ... Mori, M. (2003). Syntaxin 4 and Synip (syntaxin 4 interacting protein) regulate insulin secretion in the pancreatic β HC-9 cell. Journal of Biological Chemistry, 278(38), 36718-36725. https://doi.org/10.1074/jbc.M305114200

Syntaxin 4 and Synip (syntaxin 4 interacting protein) regulate insulin secretion in the pancreatic β HC-9 cell. / Saito, Tsugumichi; Okada, Shuichi; Yamada, Eijiro; Ohshima, Kihachi; Shimizu, Hiroyuki; Shimomura, Kenju; Sato, Minoru; Pessin, Jeffrey E.; Mori, Masatomo.

In: Journal of Biological Chemistry, Vol. 278, No. 38, 19.09.2003, p. 36718-36725.

Research output: Contribution to journalArticle

Saito, T, Okada, S, Yamada, E, Ohshima, K, Shimizu, H, Shimomura, K, Sato, M, Pessin, JE & Mori, M 2003, 'Syntaxin 4 and Synip (syntaxin 4 interacting protein) regulate insulin secretion in the pancreatic β HC-9 cell', Journal of Biological Chemistry, vol. 278, no. 38, pp. 36718-36725. https://doi.org/10.1074/jbc.M305114200
Saito, Tsugumichi ; Okada, Shuichi ; Yamada, Eijiro ; Ohshima, Kihachi ; Shimizu, Hiroyuki ; Shimomura, Kenju ; Sato, Minoru ; Pessin, Jeffrey E. ; Mori, Masatomo. / Syntaxin 4 and Synip (syntaxin 4 interacting protein) regulate insulin secretion in the pancreatic β HC-9 cell. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 38. pp. 36718-36725.
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