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

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

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 t...

Full description

Bibliographic Details
Main Authors: Li Fan, Yichao Lu, Xiulian Shen, Hong Shao, Lun Suo, Qiang Wu
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-06-01
Series:eLife
Subjects:
protocadherin
cell-adhesion kinase Pyk2
VCD
WAVE complex
cortical neuron migration
cytoskeletal dynamics
Online Access:https://elifesciences.org/articles/35242
id doaj-6af6f35a783b4501a25ba33f9c4a27f5
record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author Li Fan
Yichao Lu
Xiulian Shen
Hong Shao
Lun Suo
Qiang Wu
spellingShingle Li Fan
Yichao Lu
Xiulian Shen
Hong Shao
Lun Suo
Qiang Wu
Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice
eLife
protocadherin
cell-adhesion kinase Pyk2
VCD
WAVE complex
cortical neuron migration
cytoskeletal dynamics
author_facet Li Fan
Yichao Lu
Xiulian Shen
Hong Shao
Lun Suo
Qiang Wu
author_sort Li Fan
title Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice
title_short Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice
title_full Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice
title_fullStr Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice
title_full_unstemmed Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice
title_sort alpha protocadherins and pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via rac1 gtpase and wave complex in mice
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2018-06-01
description 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, Cakβ, Raftk, Fak2, and Cadtk), a non-receptor cell-adhesion kinase and scaffold protein downstream of Pcdhα, impairs cortical neuron migration via inactivation of the small GTPase Rac1. Thus, we define a molecular Pcdhα/WAVE/Pyk2/Rac1 axis from protocadherin cell-surface receptors to actin cytoskeletal dynamics in cortical neuron migration and dendrite morphogenesis in mouse brain.
topic protocadherin
cell-adhesion kinase Pyk2
VCD
WAVE complex
cortical neuron migration
cytoskeletal dynamics
url https://elifesciences.org/articles/35242
work_keys_str_mv AT lifan alphaprotocadherinsandpyk2kinaseregulatecorticalneuronmigrationandcytoskeletaldynamicsviarac1gtpaseandwavecomplexinmice
AT yichaolu alphaprotocadherinsandpyk2kinaseregulatecorticalneuronmigrationandcytoskeletaldynamicsviarac1gtpaseandwavecomplexinmice
AT xiulianshen alphaprotocadherinsandpyk2kinaseregulatecorticalneuronmigrationandcytoskeletaldynamicsviarac1gtpaseandwavecomplexinmice
AT hongshao alphaprotocadherinsandpyk2kinaseregulatecorticalneuronmigrationandcytoskeletaldynamicsviarac1gtpaseandwavecomplexinmice
AT lunsuo alphaprotocadherinsandpyk2kinaseregulatecorticalneuronmigrationandcytoskeletaldynamicsviarac1gtpaseandwavecomplexinmice
AT qiangwu alphaprotocadherinsandpyk2kinaseregulatecorticalneuronmigrationandcytoskeletaldynamicsviarac1gtpaseandwavecomplexinmice
_version_ 1721459672364351488
spelling doaj-6af6f35a783b4501a25ba33f9c4a27f52021-05-05T15:55:49ZengeLife Sciences Publications LtdeLife2050-084X2018-06-01710.7554/eLife.35242Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in miceLi Fan0Yichao Lu1Xiulian Shen2Hong Shao3Lun Suo4Qiang Wu5https://orcid.org/0000-0003-3841-3591Key Laboratory of Systems Biomedicine (Ministry of Education), Center for Comparative Biomedicine, Institute of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital affiliated to Shanghai Jiao Tong University Medical School, Shanghai, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaKey Laboratory of Systems Biomedicine (Ministry of Education), Center for Comparative Biomedicine, Institute of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital affiliated to Shanghai Jiao Tong University Medical School, Shanghai, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaKey Laboratory of Systems Biomedicine (Ministry of Education), Center for Comparative Biomedicine, Institute of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital affiliated to Shanghai Jiao Tong University Medical School, Shanghai, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaKey Laboratory of Systems Biomedicine (Ministry of Education), Center for Comparative Biomedicine, Institute of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital affiliated to Shanghai Jiao Tong University Medical School, Shanghai, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaKey Laboratory of Systems Biomedicine (Ministry of Education), Center for Comparative Biomedicine, Institute of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; Department of Assisted Reproduction, Shanghai Jiao Tong University Medical School, Shanghai, ChinaKey Laboratory of Systems Biomedicine (Ministry of Education), Center for Comparative Biomedicine, Institute of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital affiliated to Shanghai Jiao Tong University Medical School, Shanghai, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaDiverse 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, Cakβ, Raftk, Fak2, and Cadtk), a non-receptor cell-adhesion kinase and scaffold protein downstream of Pcdhα, impairs cortical neuron migration via inactivation of the small GTPase Rac1. Thus, we define a molecular Pcdhα/WAVE/Pyk2/Rac1 axis from protocadherin cell-surface receptors to actin cytoskeletal dynamics in cortical neuron migration and dendrite morphogenesis in mouse brain.https://elifesciences.org/articles/35242protocadherincell-adhesion kinase Pyk2VCDWAVE complexcortical neuron migrationcytoskeletal dynamics

Similar Items