CRMP‑5 interacts with actin to regulate neurite outgrowth.
CRMP‑5 interacts with actin to regulate neurite outgrowth.
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DOI：
10.3892/mmr.2015.4662
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发表时间：
2016-02
影响因子：
3.4
通讯作者：
Guo G
中科院分区：
文献类型：
--
作者：
Gong X;Tan M;Gao Y;Chen K;Guo G
CRMP家族蛋白（CRMPs）在发育中的神经系统中大量表达，介导生长锥导向、神经元极性和轴突伸长。CRMP-5已被证明在神经突生长中起关键作用。然而，CRMP-5如何调节神经突生长的详细机制仍不清楚。在目前的研究中，免疫共沉淀被用来确定CRMP-5与发育中的海马神经元的生长锥中的肌动蛋白和微管蛋白细胞骨架网络相互作用的事实。与微管相比，CRMP-5对肌动蛋白的亲和力增加。免疫细胞化学被用来鉴定CRMP-5与肌动蛋白主要在生长锥中的C-结构域和T-区共定位的事实。此外，通过siRNA对CRMP-5的遗传抑制抑制了肌动蛋白的表达、生长锥的发育和神经突的生长。CRMP-5的过表达促进了与肌动蛋白的相互作用、生长锥的发育和海马神经突的生长。总之，这些数据表明，CRMP-5能够与生长锥中的肌动蛋白细胞骨架网络相互作用，并通过这种相互作用影响生长锥发育和发育中的海马神经元中的神经突生长。
CRMP family proteins (CRMPs) are abundantly expressed in the developing nervous system mediating growth cone guidance, neuronal polarity and axon elongation. CRMP-5 has been indicated to serve a critical role in neurite outgrowth. However, the detailed mechanisms of how CRMP-5 regulates neurite outgrowth remain unclear. In the current study, co-immunoprecipitation was used to identify the fact that CRMP-5 interacted with the actin and tubulin cytoskeleton networks in the growth cones of developing hippocampal neurons. CRMP-5 exhibited increased affinity towards actin when compared with microtubules. Immunocytochemistry was used to identify the fact that CRMP-5 colocalized with actin predominantly in the C-domain and T-zone in growth cones. In addition, genetic inhibition of CRMP-5 by siRNA suppressed the expression of actin, growth cone development and neurite outgrowth. Overexpression of CRMP-5 promoted the interaction with actin, growth cone development and hippocampal neurite outgrowth. Taken together, these data suggest that CRMP-5 is able to interact with the actin cytoskeleton network in the growth cone and affect growth cone development and neurite outgrowth via this interaction in developing hippocampal neurons.