The small GTP-binding protein Rac promotes the dissociation of gelsolin from actin filaments in neutrophils
The small GTP-binding protein Rac promotes the dissociation of gelsolin from actin filaments in neutrophils
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DOI：
10.1074/jbc.273.2.805
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发表时间：
1998-01-09
影响因子：
4.8
通讯作者：
Arcaro, A
中科院分区：
文献类型：
--
作者：
Arcaro, A
凝溶胶蛋白是一种肌动蛋白丝帽蛋白，已被证明在细胞迁移中发挥关键作用。在这里，我们已经研究了参与磷酸肌醇3-激酶（PI 3-激酶）和GTP结合蛋白（G蛋白）在中性粒细胞的凝溶胶-肌动蛋白相互作用的调节。渥曼青霉素抑制PI 3激酶活性不影响N-甲酰-Met-Leu-Phe刺激中性粒细胞诱导的肌动蛋白-凝胶-索林（1：1）复合物的解离。鸟苷5 '-[γ-硫代]三磷酸（GTP γ S）间接促进肌动蛋白凝溶胶蛋白复合物在使用中性粒细胞胞质溶胶的无细胞系统中的解离，并且这种作用被Rho的GDP解离抑制剂（Rho-GDI）阻断。异源三聚体G蛋白（G（i）alpha（2）和G beta（1）gamma（2））的GTP gamma S-负载的（i）alpha（2）和beta（1）gamma（2）亚基也以Rho-GDI-敏感的方式触发肌动蛋白-凝溶胶蛋白解离。GTP负载激活Rac，但不激活Rho，诱导细胞溶质肌动蛋白凝溶胶蛋白复合物的解离。在中性粒细胞胞质溶胶中加入GTP γ S-负载的G（i）α（2）或G β（1）γ（2）可增加Rac上的鸟嘌呤核苷酸交换。这些研究结果表明，在中性粒细胞的G-蛋白偶联受体激活的Rac触发uncapping的肌动蛋白丝，独立的PI 3-激酶。
Gelsolin is an actin filament-capping protein that has been shown to play a key role in cell migration. Here we have studied the involvement of phosphoinositide 3-kinase (PI 3-kinase) and GTP-binding proteins (G-proteins) in the regulation of gelsolin-actin interactions in neutrophils. Inhibition of PI 3-kinase activity in vivo by wortmannin did not affect the dissociation of actin-gel-solin (1:1) complexes induced by neutrophil stimulation with N-formyl-Met-Leu-Phe. Guanosine 5'-[gamma-thio]triphosphate (GTP gamma S) indirectly promoted the dissociation of actin gelsolin complexes in a cell-free system using neutrophil cytosol, and this effect was blocked by the GDP dissociation inhibitor for Rho (Rho-GDI). The GTP gamma S-loaded (i) alpha(2) and the beta(1) gamma(2) subunits of heterotrimeric G-proteins (G(i) alpha(2) and G beta(1) gamma(2)) also triggered actin-gelsolin dissociation in a Rho-GDI-sensitive manner. GTP-loaded activated Rac, but not activated Rho, induced the dissociation of cytosolic actin-gelsolin complexes. The guanine nucleotide exchange on Rac was increased by addition of GTP gamma S-loaded G(i) alpha(2) or G beta(1) gamma(2) to neutrophil cytosol. These findings suggest that activation of Rac by G-protein-coupled receptors in neutrophils triggers uncapping of actin filaments, independently of PI 3-kinase.