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A Collapsin Response Mediator Protein 2 Isoform Controls Myosin II-Mediated Cell Migration and Matrix Assembly by Trapping ROCK II

机译:胶原蛋白介导的胶原蛋白2亚型控制肌球蛋白II介导的细胞迁移和基质装配,通过诱捕ROCK II

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Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two binding domains but also trapped and inhibited the kinase. CRMP-2L protein levels profoundly affected haptotactic migration and the actin-myosin cytoskeleton of carcinoma cells as well as nontransformed epithelial cell migration in a ROCK activity-dependent manner. Moreover, the ectopic expression of CRMP-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions through the inhibition of ROCK II in nonneuronal cells.
机译:胶原蛋白应答介质蛋白2(CRMP-2)被称为神经元极性和通过微管组装和贩运分化的调节器。在这里,我们显示CRMP-2被普遍表达,剪接变体(CRMP-2L)主要在非神经元细胞中的上皮细胞中表达,它调节肌球蛋白II介导的细胞功能,包括细胞迁移。虽然CRMP-2短形式(CRMP-2S)被认为是神经元细胞中Rho-GTP下游激酶ROCK的底物,但是含有2L的CRMP-2复合物不仅通过两个结合域结合ROCK II的催化域,而且还可以捕获并抑制激酶。 CRMP-2L蛋白水平以ROCK活性依赖性方式深刻影响癌细胞的触觉迁移和肌动蛋白-肌球蛋白细胞骨架以及未转化的上皮细胞迁移。此外,CRMP-2L的异位表达但不抑制-2S抑制成纤维细胞中的纤连蛋白基质组装。在这些反应的基础上,CRMP-2L调节ROCK II的激酶活性,而不调节ROCK I的激酶活性,而与GTP-RhoA水平无关。这项研究通过抑制非神经细胞中的ROCK II,提供了对CRMP-2作为肌球蛋白II介导的细胞功能控制器的新见解。

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