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

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

doi:10.1016/j.cmet.2005.11.003

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Title		The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation
Authors		Fukui, Kenji Yang, Qin Cao, Yang Takahashi, Noriko Hatakeyama, Hiroyasu Wang, Haiyan Wada, Jun Zhang, Yanling Marselli, Lorella Nammo, Takao Yoneda, Kazue Onishi, Mineki Higashiyama, Shigeki Matsuzawa, Yuji Gonzalez, Frank J Weir, Gordon C Kasai, Haruo Shimomura, Iichiro Miyagawa, Jun-ichiro Wollheim, Claes Yamagata, Kazuya show all authors [1 - 21]
Published in		Cell Metabolism. 2005, vol. 2, no. 6, p. 373-84
Abstract		Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1alpha 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-1alpha in pancreatic beta cells. Expression of collectrin was decreased in the islets of HNF-1alpha (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the beta cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca(2+) 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.
Keywords		Animals — Base Sequence — Blotting, Northern — Calcium/metabolism — Cell Line — Cloning, Molecular — DNA, Complementary/metabolism — Diabetes Mellitus, Type 2/metabolism — Disease Models, Animal — Exocytosis — Genes, Reporter — Glucose/chemistry/metabolism — Glutathione Transferase/metabolism — Growth Hormone/metabolism — Hepatocyte Nuclear Factor 1/metabolism — Humans — Immunoblotting — Immunohistochemistry — Immunoprecipitation — Insulin/metabolism/secretion — Insulin-Secreting Cells/metabolism — Insulinoma — Islets of Langerhans/cytology — Membrane Glycoproteins/metabolism — Mice — Mice, Transgenic — Microscopy, Fluorescence — Microscopy, Immunoelectron — Models, Genetic — Molecular Sequence Data — Nucleic Acid Hybridization — Oligonucleotide Array Sequence Analysis — Pancreas/metabolism — Photons — Protein Binding — RNA, Messenger/metabolism — RNA, Small Interfering/metabolism — Rats — Reverse Transcriptase Polymerase Chain Reaction — SNARE Proteins/metabolism — Time Factors — Tissue Distribution — Transcription, Genetic — Two-Hybrid System Techniques
Identifiers		DOI: 10.1016/j.cmet.2005.11.003 PMID: 16330323
Full text		Article (Published version) (916 Kb) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
Citation (ISO format)		FUKUI, Kenji et al. The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation. In: Cell Metabolism, 2005, vol. 2, n° 6, p. 373-84. doi: 10.1016/j.cmet.2005.11.003 https://archive-ouverte.unige.ch/unige:34529