Scinderin-derived actin-binding peptides inhibit Ca2+- and GTP gamma S-dependent exocytosis in mouse pancreatic beta-cells

Using capacitance measurements, we have explored the effects of three diffe rent scinderin actin-binding peptides (SC77-89; Sc138-146; SC511-523) on Ca 2+- and GTP gamma S-induced exocytosis in single mouse pancreatic beta-cell s. SC77-89 (10 mu M) reduced exocytosis by 43% in whole-cell experiments in which secretion was triggered by intracellular dialysis with a Ca2+-EGTA b uffer with a free Ca2+ concentration of 2 mu M. A more pronounced reduction of the rate of exocytosis was observed with SC138-146 (72%) but not with S c511-523 (39%). Sc138-146 also reduced depolarisation-induced exocytosis by 61% without affecting the whole-cell Ca2+ current. When exocytosis was tri ggered by infusion of GTP gamma S, all scinderin-binding peptides reduced e xocytosis by 59-75%. These data suggest that scinderin might be important f or controlling cortical actin network dynamics in mouse pancreatic beta-cel ls and that scinderin-induced cortical filamentous actin disassembly is req uired for insulin secretion. (C) 2000 Elsevier Science B.V. All rights rese rved.