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 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) regulatory complex (WRC). 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 Thus, we define a molecular Pcdhα/WRC/Pyk2/Rac1 axis from Pcdh cell- surface receptors to actin cytoskeletal dynamics in cortical neuron migration in mousebrain.
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.
Reviewing Editor
- Jeremy Nathans, Johns Hopkins University School of Medicine, United States
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).
Version history
- Received: January 19, 2018
- Accepted: June 11, 2018
- Accepted Manuscript published: June 18, 2018 (version 1)
- Accepted Manuscript updated: June 19, 2018 (version 2)
- 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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Further reading
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Probing memory of a complex visual image within a few hundred milliseconds after its disappearance reveals significantly greater fidelity of recall than if the probe is delayed by as little as a second. Classically interpreted, the former taps into a detailed but rapidly decaying visual sensory or ‘iconic’ memory (IM), while the latter relies on capacity-limited but comparatively stable visual working memory (VWM). While iconic decay and VWM capacity have been extensively studied independently, currently no single framework quantitatively accounts for the dynamics of memory fidelity over these time scales. Here, we extend a stationary neural population model of VWM with a temporal dimension, incorporating rapid sensory-driven accumulation of activity encoding each visual feature in memory, and a slower accumulation of internal error that causes memorized features to randomly drift over time. Instead of facilitating read-out from an independent sensory store, an early cue benefits recall by lifting the effective limit on VWM signal strength imposed when multiple items compete for representation, allowing memory for the cued item to be supplemented with information from the decaying sensory trace. Empirical measurements of human recall dynamics validate these predictions while excluding alternative model architectures. A key conclusion is that differences in capacity classically thought to distinguish IM and VWM are in fact contingent upon a single resource-limited WM store.
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- Neuroscience
Our ability to recall details from a remembered image depends on a single mechanism that is engaged from the very moment the image disappears from view.