Aberrant expression of LIMK1 impairs neuronal migration during neocortex development

被引：9

作者：

Xie, Jiongfang ^{[1
]}

Li, Xuzhao ^{[1
]}

Zhang, Wei ^{[1
]}

Chai, Xuejun ^{[1
]}

Huang, Yingxue ^{[1
]}

Li, Kaikai ^{[1
]}

Cheng, Xinran ^{[1
]}

Zhao, Shanting ^{[1
]}

机构：

[1] Northwest A&F Univ, Coll Vet Med, 22 Xinong Rd, Yangling 712100, Shaanxi, Peoples R China

来源：

HISTOCHEMISTRY AND CELL BIOLOGY | 2017年 / 147卷 / 04期

关键词：

LIMK1; Neuronal migration; In utero electroporation; Cofilin phosphorylation; Actin cytoskeleton; DEVELOPING CEREBRAL-CORTEX; KINASE; COFILIN PHOSPHORYLATION; WILLIAMS-SYNDROME; ACTIN DYNAMICS; BRAIN; CELLS; REORGANIZATION; POLARIZATION; ORGANIZATION;

D O I：

10.1007/s00418-016-1514-8

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Neuronal migration is essential for the formation of cortical layers, and proper neuronal migration requires the coordination of cytoskeletal regulation. LIMK1 is a serine/threonine protein kinase that mediates actin dynamics by regulating actin depolymerization factor/cofilin. However, the role of LIMK1 in neuronal migration and its potential mechanism remains elusive. Here, we found that using the in utero electroporation to overexpress LIMK1 and its mutants, constitutively active LIMK1 (LIMK1-CA) and dominant-negative LIMK1 (LIMK1-DN), impaired neuronal migration in the embryonic mouse brain. In addition, the aberrant expression of LIMK1-WT and LIMK1-CA induced abnormal branching and increased the length of the leading process, while LIMK1-DN-transfected neurons gave rise to two leading processes. Furthermore, the co-transfection of LIMK1-CA and cofilin-S3A partially rescued the migration deficiency and fully rescued the morphological changes in migrating neurons induced by LIMK1-CA. Our results indicated that LIMK1 negatively regulated neuronal migration by affecting the neuronal cytoskeleton and that its effects were partly mediated by cofilin phosphorylation.

引用

页码：471 / 479

页数：9

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