HEMOSTATIC, INFLAMMATORY, AND FIBROBLAST RESPONSES ARE BLUNTED IN MICE LACKING GELSOLIN
HEMOSTATIC, INFLAMMATORY, AND FIBROBLAST RESPONSES ARE BLUNTED IN MICE LACKING GELSOLIN
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DOI：
10.1016/0092-8674(95)90369-0
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发表时间：
1995-04-07
期刊：
影响因子：
64.5
通讯作者：
KWIATKOWSKI, DJ
中科院分区：
文献类型：
--
作者：
WITKE, W;SHARPE, AH;KWIATKOWSKI, DJ
凝溶胶蛋白是一种分子量为82 kDa的肌动蛋白结合蛋白，在体外具有很强的肌动蛋白切割活性。为了研究凝溶胶蛋白在体内的功能，转基因gelsolinnull（Osn（-））小鼠，并发现有正常的胚胎发育和寿命。然而，Gsn（-）小鼠的血小板形状变化减少，导致出血时间延长。中性粒细胞在体内和体外迁移到腹膜渗出液中被延迟。Gsn（-）真皮成纤维细胞有过多的肌动蛋白应力纤维，比野生型成纤维细胞迁移更慢，但在体外具有增加的收缩性。这些观察结果确立了在参与应激反应如止血、炎症和伤口愈合的细胞类型中快速运动反应对凝溶胶蛋白的需求。无论是凝溶胶蛋白，也没有其他蛋白质具有类似的肌动蛋白切割活性的表达在早期胚胎细胞，表明肌动蛋白丝动力学的这种机制是不是必不可少的运动在早期胚胎发生。
Gelsolin, an 82 kDa actin-binding protein, has potent actin filament-severing activity in vitro. To investigate the in vivo function of gelsolin, transgenic gelsolinnull (Osn(-)) mice were generated and found to have normal embryonic development and longevity. However, platelet shape changes are decreased in Gsn(-) mice, causing prolonged bleeding times. Neutrolphil migration in vivo into peritoneal exudates and in vitro is delayed. Gsn(-) dermal fibroblasts have excessive actin stress fibers and migrate more slowly than wildtype fibroblasts, but have increased contractility in vitro. These observations establish the requirement of gelsolin for rapid motile responses in cell types involved in stress responses such as hemostasis, inflammation, and wound healing. Neither gelsolin nor other proteins with similar actin filament-severing activity are expressed in early embryonic cells, indicating that this mechanism of actin filament dynamics is not essential for motility during early embryogenesis.