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

Abstract
Data availability
Article and author information
Metrics

Abstract

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 WASP or Wasf) complex. In addition, overexpression of proline-rich tyrosine kinase 2 (Pyk2, also known as Ptk2b, Cakb, Raftk, Fak2, and Cadtk), a non-receptor cell-adhesion kinase and scaffold protein downstream of Pcdha, impairs cortical neuron migration via inactivation of the small GTPase Rac1. Thus, we define a molecular Pcdha/WAVE/Pyk2/Rac1 axis from protocadherin cell-surface receptors to actin cytoskeletal dynamics in cortical neuron migration in mouse brain.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.

Article and author information

Author details

Li Fan

Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Yichao Lu

Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Xiulian Shen

Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Hong Shao

Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Lun Suo

Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Qiang Wu

Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China

For correspondence
qiangwu@sjtu.edu.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3841-3591

Funding

National Natural Science Foundation of China (31630039)

Qiang Wu

National Natural Science Foundation of China (91640118)

Qiang Wu

National Natural Science Foundation of China (31470820)

Qiang Wu

Ministry of Science and Technology of the People's Republic of China (2017YFA0504203)

Qiang Wu

The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experimentation: All procedures involving animals were in accordance with the Shanghai Municipal Guide for the care and use of Laboratory Animals, and approved by the Shanghai Jiao Tong University Animal Care and Use Committee (protocol #: 1602029).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.