The HNF-1alpha-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 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.
Yamagata
K
K
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. kazu@imed.med.osaka-u.ac.jp
Nammo
T
T
Sato
Y
Y
Saisho
K
K
Shoda
H
H
Fukui
K
K
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005089:Exocytosis / Q000502:physiology; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D050600:SNARE Proteins / Q000378:metabolism*
C429534:CLTRN protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D007328:Insulin; D008562:Membrane Glycoproteins; D050600:SNARE Proteins