The HNF-1alpha-SNARE connection

• Published in: Diabetes, obesity & metabolism Vol. 9 Suppl 2; pp. 40 - 45
• Main Authors: Yamagata, K, Nammo, T, Sato, Y, Saisho, K, Shoda, H, Fukui, K
• Format: Journal Article
• Language: English
• Published: England 01.11.2007
• Subjects: Animals; Diabetes Mellitus, Type 2 - metabolism; Disease Models, Animal; Exocytosis - physiology; Hepatocyte Nuclear Factor 1-alpha - metabolism; Humans; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - metabolism; Membrane Glycoproteins - metabolism; Mice; Mutation; SNARE Proteins - metabolism
• ISSN: 1462-8902; 1463-1326

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 beta-cells. We previously reported that heterozygous mutations of the hepatocyte nuclear factor (HNF)-1alpha 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-1alpha in pancreatic beta-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.