The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation

Kenji Fukui, Qin Yang, Yang Cao, Noriko Takahashi, Hiroyasu Hatakeyama, Haiyan Wang, Jun Wada, Yanling Zhang, Lorella Marselli, Takao Nammo, Kazue Yoneda, Mineki Onishi, Shigeki Higashiyama, Yuji Matsuzawa, Frank J. Gonzalez, Gordon C. Weir, Haruo Kasai, Iichiro Shimomura, Jun Ichiro Miyagawa, Claes B. WollheimKazuya Yamagata

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Abstract

Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1α cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1α in pancreatic β cells. Expression of collectrin was decreased in the islets of HNF-1α (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the β cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca2+ influx. Conversely, suppression of collectrin attenuated insulin secretion. Collectrin bound to SNARE complexes by interacting with snapin, a SNAP-25 binding protein, and facilitated SNARE complex formation. Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis.

Original languageEnglish
Pages (from-to)373-384
Number of pages12
JournalCell Metabolism
Volume2
Issue number6
DOIs
Publication statusPublished - Dec 2005

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Fukui, K., Yang, Q., Cao, Y., Takahashi, N., Hatakeyama, H., Wang, H., Wada, J., Zhang, Y., Marselli, L., Nammo, T., Yoneda, K., Onishi, M., Higashiyama, S., Matsuzawa, Y., Gonzalez, F. J., Weir, G. C., Kasai, H., Shimomura, I., Miyagawa, J. I., ... Yamagata, K. (2005). The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation. Cell Metabolism, 2(6), 373-384. https://doi.org/10.1016/j.cmet.2005.11.003