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CRMP-5与肌动蛋白相互作用以调节神经突生长。

CRMP‑5 interacts with actin to regulate neurite outgrowth.

作者信息

Gong Xiaobing, Tan Minghui, Gao Yuan, Chen Keen, Guo Guoqing

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China.

Department of Anatomy, Medical College of Jinan University, Guangzhou, Guangdong 510630, P.R. China.

出版信息

Mol Med Rep. 2016 Feb;13(2):1179-85. doi: 10.3892/mmr.2015.4662. Epub 2015 Dec 9.

Abstract

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.

摘要

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。已有研究表明CRMP-5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。在本研究中,采用免疫共沉淀法确定CRMP-5与发育中海马神经元生长锥中的肌动蛋白和微管蛋白细胞骨架网络相互作用。与微管相比,CRMP-5对肌动蛋白的亲和力增加。采用免疫细胞化学法确定CRMP-5主要在生长锥的C结构域和T区与肌动蛋白共定位。此外,通过小干扰RNA对CRMP-5进行基因抑制可抑制肌动蛋白的表达、生长锥发育和神经突生长。CRMP-5的过表达促进了与肌动蛋白的相互作用、生长锥发育和海马神经突生长。综上所述,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发育中海马神经元的生长锥发育和神经突生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fd2/4732841/127d6db1466b/MMR-13-02-1179-g00.jpg

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