CRMP4 regulates dendritic growth and maturation via the interaction with actin cytoskeleton in cultured hippocampal neurons

CRMP4 regulates dendritic growth and maturation via the interaction with actin cytoskeleton in cultured hippocampal neurons
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CRMP4 通过与培养的海马神经元中肌动蛋白细胞骨架的相互作用来调节树突生长和成熟

DOI:
10.1016/j.brainresbull.2016.06.008
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发表时间:
2016-06-01
影响因子:
3.8
通讯作者:
Lin, Hongsheng
Lin, Hongsheng
中科院分区:
医学3区
文献类型:
--
作者:
Cha, Caihui;Zhang, Jifeng;Lin, Hongsheng

文献摘要

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CRMP家族蛋白(CRMPs)对于神经系统发育中的神经突生长和成熟至关重要。然而,CRMP亚型的独特作用仍有待阐明,特别是在树突发育。在这里,我们表明,CRMP 4是足够的和必要的树突生长和成熟培养海马神经元。CRMP 4的过表达促进和CRMP 4的基因敲低抑制树突尖端的数量、树突总长度、棘密度和微型兴奋性突触电流的频率而不是振幅。通过GST-pulldown分析,我们发现CRMP 4通过其C-末端区域与肌动蛋白细胞骨架相互作用,而不是通过N-末端。CRMP 4肌动蛋白相互作用区的过表达促进树突状细胞的生长和成熟的CRMP 4野生型。综上所述,这些结果表明,CRMP 4通过与海马神经元中肌动蛋白细胞骨架的相互作用参与树突发育。(C)2016 Elsevier Inc. All rights reserved.
CRMP family proteins (CRMPs) are critical for neurite outgrowth and maturation in the developing nervous system. However, the distinct roles of CRMP isoforms remain to be elucidated, especially in dendritic development. Here, we show that CRMP4 is sufficient and necessary for dendritic growth and maturation in cultured hippocampal neurons. Overexpression of CRMP4 promotes and genetic knockdown of CRMP4 inhibits the amount of dendritic tips, total dendritic length, spine density, and the frequency but not amplitude of miniature excitatory synaptic current. By GST-pulldown assay, we reveal that CRMP4 interacts with actin cytoskeleton by its C-terminal region, but not by N-terminal. Overexpression of actin-interacting region of CRMP4 promoted dendritic growth and maturation as CRMP4 wildtype. Taken together, these results suggest that CRMP4 is involved in dendritic development via the interaction with actin cytoskeleton in hippocampal neurons. (C) 2016 Elsevier Inc. All rights reserved.