CRMP4 and CRMP2 Interact to Coordinate Cytoskeleton Dynamics, Regulating Growth Cone Development and Axon Elongation.
CRMP4 and CRMP2 Interact to Coordinate Cytoskeleton Dynamics, Regulating Growth Cone Development and Axon Elongation.
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CRMP4 和 CRMP2 相互作用以协调细胞骨架动力学，调节生长锥发育和轴突伸长。
DOI：
10.1155/2015/947423
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发表时间：
2015
影响因子：
3.1
通讯作者：
Guo G
中科院分区：
文献类型：
--
作者：
Tan M;Cha C;Ye Y;Zhang J;Li S;Wu F;Gong S;Guo G
细胞骨架动力学是支撑许多基本细胞过程的关键现象。坍缩反应中介蛋白（CRMPs）在发育中的神经系统中高度表达，介导生长锥引导、神经元极性和轴突伸长。然而，CRMPs是否以及如何与微管和肌动蛋白协调的细胞骨架动力学相关联仍然未知。在这项研究中，我们证明了CRMP2和CRMP4在体外与微管蛋白和肌动蛋白相互作用，并在生长锥发育的过渡区与细胞骨架共定位。CRMP2和CRMP4还相互协调作用，促进生长锥发育和轴突伸长。CRMP2基因沉默增强，而CRMP2过表达抑制CRMP4基因敲低对轴突发育的抑制作用。此外，敲低CRMP2或过表达截断的CRMP2可逆转CRMP4的促进作用。截断的CRMP2或缺乏细胞骨架相互作用结构域的CRMP4过表达，抑制了CRMP的促进作用。这些数据表明，CRMP2和CRMP4形成复合物以桥接微管和肌动蛋白，从而协同调节生长锥发育和轴突伸长。
Cytoskeleton dynamics are critical phenomena that underpin many fundamental cellular processes. Collapsin response mediator proteins (CRMPs) are highly expressed in the developing nervous system, mediating growth cone guidance, neuronal polarity, and axonal elongation. However, whether and how CRMPs associate with microtubules and actin coordinated cytoskeletal dynamics remain unknown. In this study, we demonstrated that CRMP2 and CRMP4 interacted with tubulin and actin in vitro and colocalized with the cytoskeleton in the transition-zone in developing growth cones. CRMP2 and CRMP4 also interacted with one another coordinately to promote growth cone development and axonal elongation. Genetic silencing of CRMP2 enhanced, whereas overexpression of CRMP2 suppressed, the inhibitory effects of CRMP4 knockdown on axonal development. In addition, knockdown of CRMP2 or overexpression of truncated CRMP2 reversed the promoting effect of CRMP4. With the overexpression of truncated CRMP2 or CRMP4 lacking the cytoskeleton interaction domain, the promoting effect of CRMP was suppressed. These data suggest a model in which CRMP2 and CRMP4 form complexes to bridge microtubules and actin and thus work cooperatively to regulate growth cone development and axonal elongation.
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影响因子：
5.3
作者：
Kandan, Nicholas M.;Pigino, Gustavo F.;Brady, Scott T.;Lazarov, Orly;Binder, Lester I.;Morfini, Gerardo A.
通讯作者：
Morfini, Gerardo A.
影响因子：
4.8
作者：
Khazaei, Mohamad R.;Girouard, Marie-Pier;Fournier, Alyson E.
通讯作者：
Fournier, Alyson E.
影响因子：
5.3
作者：
Alabed, Yazan Z.;Pool, Madeline;Fournier, Alyson E.
通讯作者：
Fournier, Alyson E.
影响因子：
5.3
作者：
Alabed, Yazan Z.;Pool, Madeline;Fournier, Alyson E.
通讯作者：
Fournier, Alyson E.
影响因子：
21.3
作者：
Fukata, Y;Itoh, TJ;Kaibuchi, K
通讯作者：
Kaibuchi, K