G-protein betagamma-binding domains regulate insulin exocytosis in clonal pancreatic beta-cells.
We have tested the putative role of G-protein beta-subunits in insulin exocytosis by transient expression of betagamma-binding proteins targeted to the plasma membrane. The PH domain of the G-protein-linked receptor kinase 2 fused to the transmembrane domain of a cell surface receptor and the alpha-subunit of the retinal G-protein transducin inhibited stimulated insulin release from intact and permeabilised HIT-T15 cells. This effect cannot be imputed to an increase in free Galpha, as the RGS protein RGS3 did not reverse this effect. Among the isoforms of Gbeta examined, Gbeta2 was detected on the plasma membrane by confocal immunomicroscopy. These observations suggest a role for G-protein betagamma-subunits in insulin exocytosis.
Zhang
H
H
Département de Médecine Interne, Centre Médical Universitaire, Geneva, Switzerland.
Yasrebi-Nejad
H
H
Lang
J
J
D000818:Animals; D001665:Binding Sites; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002999:Clone Cells; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D054769:G-Protein-Coupled Receptor Kinase 2; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015293:Transducin / Q000235:genetics / Q000378:metabolism; D051552:beta-Adrenergic Receptor Kinases
D016827:CD8 Antigens; D007328:Insulin; D011994:Recombinant Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D017868:Cyclic AMP-Dependent Protein Kinases; C496569:Grk2 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; D019204:GTP-Binding Proteins; D015293:Transducin; D002118:Calcium