Scaife Robin M, Job Didier, Langdon Wallace Y
Department of Pathology, University of Western Australia, Crawley, WA 6009, Australia.
Mol Biol Cell. 2003 Nov;14(11):4605-17. doi: 10.1091/mbc.e02-11-0739. Epub 2003 Sep 5.
A number of key cellular functions, such as morphological differentiation and cell motility, are closely associated with changes in cytoskeletal dynamics. Many of the principal signaling components involved in actin cytoskeletal dynamics have been identified, and these have been shown to be critically involved in cell motility. In contrast, signaling to microtubules remains relatively uncharacterized, and the importance of signaling pathways in modulation of microtubule dynamics has so far not been established clearly. We report here that the Rho-effector ROCK and the multiadaptor proto-oncoprotein Cbl can profoundly affect the microtubule cytoskeleton. Simultaneous inhibition of these two signaling molecules induces a dramatic rearrangement of the microtubule cytoskeleton into microtubule bundles. The formation of these microtubule bundles, which does not involve signaling by Rac, Cdc42, Crk, phosphatidylinositol 3-kinase, and Abl, is sufficient to induce distinct neurite-like extensions in NIH 3T3 fibroblasts, even in the absence of microfilaments. This novel microtubule-dependent function that promotes neurite-like extensions is not dependent on net changes in microtubule polymerization or stabilization, but rather involves selective elongation and reorganization of microtubules into long bundles.
许多关键的细胞功能，如形态分化和细胞运动，都与细胞骨架动力学的变化密切相关。许多参与肌动蛋白细胞骨架动力学的主要信号成分已被确定，并且这些成分已被证明在细胞运动中起着关键作用。相比之下，向微管的信号传导仍相对未被充分了解，并且信号通路在调节微管动力学中的重要性迄今尚未明确确立。我们在此报告，Rho效应器ROCK和多接头原癌蛋白Cbl可深刻影响微管细胞骨架。同时抑制这两种信号分子会导致微管细胞骨架戏剧性地重排为微管束。这些微管束的形成不涉及Rac、Cdc42、Crk、磷脂酰肌醇3激酶和Abl的信号传导，即使在没有微丝的情况下，也足以在NIH 3T3成纤维细胞中诱导出明显的神经突样延伸。这种促进神经突样延伸的新型微管依赖性功能不依赖于微管聚合或稳定的净变化，而是涉及微管选择性地伸长并重组为长束。
