Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice
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
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
© 2018, Fan et al.
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.
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