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

Fukui, Kenji
Yang, Qin
Cao, Yang
Takahashi, Noriko
Hatakeyama, Hiroyasu
Wada, Jun
Zhang, Yanling
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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 AnimalsBase SequenceBlotting, NorthernCalcium/metabolismCell LineCloning, MolecularDNA, Complementary/metabolismDiabetes Mellitus, Type 2/metabolismDisease Models, AnimalExocytosisGenes, ReporterGlucose/chemistry/metabolismGlutathione Transferase/metabolismGrowth Hormone/metabolismHepatocyte Nuclear Factor 1/metabolismHumansImmunoblottingImmunohistochemistryImmunoprecipitationInsulin/metabolism/secretionInsulin-Secreting Cells/metabolismInsulinomaIslets of Langerhans/cytologyMembrane Glycoproteins/metabolismMiceMice, TransgenicMicroscopy, FluorescenceMicroscopy, ImmunoelectronModels, GeneticMolecular Sequence DataNucleic Acid HybridizationOligonucleotide Array Sequence AnalysisPancreas/metabolismPhotonsProtein BindingRNA, Messenger/metabolismRNA, Small Interfering/metabolismRatsReverse Transcriptase Polymerase Chain ReactionSNARE Proteins/metabolismTime FactorsTissue DistributionTranscription, GeneticTwo-Hybrid System Techniques
PMID: 16330323
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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

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Deposited on : 2014-02-28

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