The HNF‐1α‐SNARE connection

Maturity‐onset diabetes of the young (MODY) is a monogenic form of type 2 diabetes mellitus that is characterized by impairment of glucose‐stimulated insulin secretion from pancreatic β‐cells. We previously reported that heterozygous mutations of the hepatocyte nuclear factor (HNF)‐1α gene cause a form of MODY (MODY3). We have subsequently found that collectrin, a recently cloned kidney‐specific gene of unknown function, is a novel target of HNF‐1α in pancreatic β‐cells. In addition, we have demonstrated that collectrin forms a complex with the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) complex by direct interaction with snapin, a protein that is thought to be involved in neurotransmission by binding to synaptosomal‐associated protein, 25 KD (SNAP25). Collectrin favours the formation of SNARE complexes and controls insulin exocytosis.

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