Scinderin-derived actin-binding peptides inhibit Ca2+- and GTPγS-dependent exocytosis in mouse pancreatic β-cells

被引:19
作者
Bruun, TZ [1 ]
Hoy, M [1 ]
Gromada, J [1 ]
机构
[1] Novo Nordisk AS, Islet Discovery Res, Lab Islet Cell Physiol, DK-2880 Bagsvaerd, Denmark
关键词
cytoskeleton; exocytosis; insulin; scinderin;
D O I
10.1016/S0014-2999(00)00602-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Using capacitance measurements, we have explored the effects of three different scinderin actin-binding peptides (SC77-89; Sc138-146; SC511-523) on Ca2+- and GTP gamma S-induced exocytosis in single mouse pancreatic beta-cells. 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 buffer 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 Sc511-523 (39%). Sc138-146 also reduced depolarisation-induced exocytosis by 61% without affecting the whole-cell Ca2+ current. When exocytosis was triggered by infusion of GTP gamma S, 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. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:221 / 224
页数:4
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