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

  1. Li Fan
  2. Yichao Lu
  3. Xiulian Shen
  4. Hong Shao
  5. Lun Suo
  6. Qiang Wu  Is a corresponding author
  1. Shanghai Jiao Tong University, China
Research Article
  • Cited 15
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Cite this article as: eLife 2018;7:e35242 doi: 10.7554/eLife.35242

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

  1. Li Fan

    Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Yichao Lu

    Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Xiulian Shen

    Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Hong Shao

    Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Lun Suo

    Center for Comparative Biomedicine, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. 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.
    ORCID icon "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).

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: January 19, 2018
  2. Accepted: June 11, 2018
  3. Accepted Manuscript published: June 18, 2018 (version 1)
  4. Accepted Manuscript updated: June 19, 2018 (version 2)
  5. Version of Record published: July 16, 2018 (version 3)

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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