Scinderin-derived actin-binding peptides inhibit Ca(2+)- and GTPgammaS-dependent exocytosis in mouse pancreatic beta-cells.
Using capacitance measurements, we have explored the effects of three different scinderin actin-binding peptides (Sc(77-89); Sc(138-146); Sc(511-523)) on Ca(2+)- and GTPgammaS-induced exocytosis in single mouse pancreatic beta-cells. Sc(77-89) (10 microM) reduced exocytosis by 43% in whole-cell experiments in which secretion was triggered by intracellular dialysis with a Ca(2+)-EGTA buffer with a free Ca(2+) concentration of 2 microM. A more pronounced reduction of the rate of exocytosis was observed with Sc(138-146) (72%) but not with Sc(511-523) (39%). Sc(138-146) also reduced depolarisation-induced exocytosis by 61% without affecting the whole-cell Ca(2+) current. When exocytosis was triggered by infusion of GTPgammaS, all scinderin-binding peptides reduced exocytosis by 59-75%. These data suggest that scinderin might be important for controlling cortical actin network dynamics in mouse pancreatic beta-cells and that scinderin-induced cortical filamentous actin disassembly is required for insulin secretion.
Bruun
T Z
TZ
Islet Discovery Research, Laboratory of Islet Cell Physiology, Building 1KS.18-23, Novo Nordisk A/S, Novo Alle, DK-2880 Bagsvaerd, Denmark.
Høy
M
M
Gromada
J
J
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D005089:Exocytosis / Q000187:drug effects*; D018260:Gelsolin; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000037:antagonists & inhibitors*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000494:pharmacology*; D018408:Patch-Clamp Techniques
D018260:Gelsolin; D007328:Insulin; D008840:Microfilament Proteins; C065395:scinderin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002118:Calcium