The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion.
The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion.
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DOI：
10.1083/jcb.200308055
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发表时间：
2004-05-10
期刊：
影响因子：
--
通讯作者：
Koleske AJ
中科院分区：
文献类型：
--
作者：
Miller AL;Wang Y;Mooseker MS;Koleske AJ
微管（MT）通过促进肌动蛋白依赖的膜在细胞前缘的突出来帮助建立和维持细胞极性，但在此过程中介导肌动蛋白和MT之间的串扰的分子机制尚不清楚。我们证明，与纤维连接蛋白粘附后，动态板状突起所需的非受体酪氨酸激酶相关的基因（Arg）。与野生型成纤维细胞相比，Arg − / −成纤维细胞表现出减少的板状脂质动力学，并且这种缺陷可以通过Arg-黄色荧光蛋白融合物的再表达来挽救。我们发现，精氨酸可以结合MT与高亲和力和交联丝状肌动蛋白（F-actin）束和MT在体外。MT集中并插入Arg诱导的富含F-肌动蛋白的细胞突起中。Arg需要其F-肌动蛋白结合结构域和MT-结合结构域来挽救arg − / −成纤维细胞的板状伪足动力学缺陷。这些研究结果表明，精氨酸可以介导的F-肌动蛋白和MT之间的物理接触在细胞周边，这种交联活性是必需的精氨酸调节成纤维细胞中的lamellipodial动力学。
Microtubules (MTs) help establish and maintain cell polarity by promoting actin-dependent membrane protrusion at the leading edge of the cell, but the molecular mechanisms that mediate cross-talk between actin and MTs during this process are unclear. We demonstrate that the Abl-related gene (Arg) nonreceptor tyrosine kinase is required for dynamic lamellipodial protrusions after adhesion to fibronectin. arg − / − fibroblasts exhibit reduced lamellipodial dynamics as compared with wild-type fibroblasts, and this defect can be rescued by reexpression of an Arg-yellow fluorescent protein fusion. We show that Arg can bind MTs with high affinity and cross-link filamentous actin (F-actin) bundles and MTs in vitro. MTs concentrate and insert into Arg-induced F-actin–rich cell protrusions. Arg requires both its F-actin–binding domains and its MT-binding domain to rescue the defects in lamellipodial dynamics of arg − / − fibroblasts. These findings demonstrate that Arg can mediate physical contact between F-actin and MTs at the cell periphery and that this cross-linking activity is required for Arg to regulate lamellipodial dynamics in fibroblasts.
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