Gelsolin is a downstream effector of rac for fibroblast motility
Gelsolin is a downstream effector of rac for fibroblast motility
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DOI：
10.1093/emboj/17.5.1362
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发表时间：
1998-03-02
期刊：
影响因子：
11.4
通讯作者：
Kwiatkowski, DJ
中科院分区：
文献类型：
--
作者：
Azuma, T;Witke, W;Kwiatkowski, DJ
Rac 是 GTPases rho 家族的成员，当激活时会传递信号，导致成纤维细胞中基于肌动蛋白的膜发生褶皱。与野生型成纤维细胞相比，凝溶胶蛋白无效 (Gsn(-)) 真皮成纤维细胞对血清或 EGF 刺激（通过 rac 发出信号）的皱褶反应显着降低。缓激肽诱导的丝状伪足形成（归因于 cdc42 的激活）在两种细胞类型中相似，野生型成纤维细胞在平移运动过程中表现出典型的板状伪足延伸，而 Gsn(-) 细胞使用类似丝状伪足的结构，移动速度慢 50%，多个 Gsn(-) 组织以及 Gsn(-) 成纤维细胞 过表达 rac，但不过度表达 cdc42 或 rho，5 倍，通过稳定转染或腺病毒在 Gsn(-) 成纤维细胞中重新表达凝溶胶蛋白，可将扰动反应、翻译运动和 rac 表达恢复正常，在浴细胞类型中，Rac 在 EGF 刺激后迁移到细胞膜，凝溶胶蛋白是 rac 介导的肌动蛋白动力学的重要效应物，作用于下游 rac募集到膜上。
Rac, a member of the rho family of GTPases, when activated transmits signals leading to actin-based membrane ruffling in fibroblasts. Compared with wild-type fibroblasts, gelsolin null (Gsn(-)) dermal fibroblasts have a markedly reduced ruffling response to serum or EGF stimulation, which signal through rac. Bradykinin-induced filopodial formation, attributable to activation of cdc42, is similar in both cell types, Wild-type fibroblasts exhibit typical lamellipodial extension during translational locomotion, whereas Gsn(-) cells move 50 % slower using structures resembling filopodia, Multiple Gsn(-) tissues as well as Gsn(-) fibroblasts over-express rac, but not cdc42 or rho, 5-fold, Re-expression of gelsolin in Gsn(-) fibroblasts by stable transfection or adenovirus reverts the ruffling response, translational motility and rac expression to normal, Rac migrates to the cell membrane following EGF stimulation in bath cell types, Gelsolin is an essential effector of rac-mediated actin dynamics, acting downstream of rac recruitment to the membrane.