Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice

被引：45

作者：

Fan, Li ^{[1
,2
,3
,5
]}

Lu, Yichao ^{[1
,2
,3
]}

Shen, Xiulian ^{[1
,2
,3
]}

Shao, Hong ^{[1
,2
,3
]}

Suo, Lun ^{[1
,4
]}

Wu, Qiang ^{[1
,2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Inst Syst Biomed, Ctr Comparat Biomed,Minist Educ,Key Lab Syst Biom, Shanghai, Peoples R China

[2] Shanghai Jiao Tong Univ, Med Sch, Renji Hosp, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Med Sch, Dept Assisted Reprod, Shanghai, Peoples R China

[5] Sloan Kettering Inst, Dev Biol Program, New York, NY USA

来源：

ELIFE | 2018年 / 7卷

基金：

中国国家自然科学基金;

关键词：

DEVELOPING CEREBRAL-CORTEX; ARP2/3; COMPLEX; CELL-MIGRATION; GAMMA-PROTOCADHERINS; N-WASP; GENE; MOUSE; ARCHITECTURE; DIVERSITY; ADHESION;

D O I：

10.7554/eLife.35242

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Diverse clustered protocadherins are thought to function in neurite morphogenesis and neuronal connectivity in the brain. Here, we report that the protocadherin alpha (Pcdha) gene cluster regulates neuronal migration during cortical development and cytoskeletal dynamics in primary cortical culture through the WAVE (Wiskott-Aldrich syndrome family verprolin homologous protein, also known as Wasf) complex. In addition, overexpression of proline-rich tyrosine kinase 2 (Pyk2, also known as Ptk2b, Cak beta, Raftk, Fak2, and Cadtk), a non-receptor cell-adhesion kinase and scaffold protein downstream of Pcdh a, impairs cortical neuron migration via inactivation of the small GTPase Rac1. Thus, we define a molecular Pcdh alpha/WAVE/Pyk2/Rac1 axis from protocadherin cell-surface receptors to actin cytoskeletal dynamics in cortical neuron migration and dendrite morphogenesis in mouse brain.

引用

页数：26

共 62 条

[1] AUTORADIOGRAPHIC STUDY OF CELL MIGRATION DURING HISTOGENESIS OF CEREBRAL CORTEX IN MOUSE [J].