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Abstract

Oligodendrocyte progenitor cells (OPCs) express protocadherin 15 (Pcdh15), a member of the cadherin superfamily of transmembrane proteins. Little is known about the function of Pcdh15 in the central nervous system (CNS), however, Pcdh15 expression can predict glioma aggression and promote the separation of embryonic human OPCs immediately following a cell division. Herein, we show that Pcdh15 knockdown significantly increases extracellular signal-related kinase (ERK) phosphorylation and activation to enhance OPC proliferation in vitro. Furthermore, Pcdh15 knockdown elevates Cdc42-Arp2/3 signalling and impairs actin kinetics, reducing the frequency of lamellipodial extrusion and slowing filopodial withdrawal. Pcdh15 knockdown also reduces the number of processes supported by each OPC and new process generation. Our data indicate that Pcdh15 is a critical regulator of OPC proliferation and process motility, behaviours that characterise the function of these cells in the healthy CNS, and provide mechanistic insight into the role that Pcdh15 might play in glioma progression.

Item Type:	Article
Authors/Creators:	Zhen, Y and Cullen, CL and Ricci, R and Summers, BS and Rehman, S and Ahmed, ZM and Foster, AY and Emery, B and Gasperini, R and Young, KM
Keywords:	protocadherin 15, oligodendrocyte progenitor cell, glioma, proliferation, cytoskeleton
Journal or Publication Title:	Communications Biology
Publisher:	Nature Publishing Group
ISSN:	2399-3642
DOI / ID Number:	10.1038/s42003-022-03470-1
Copyright Information:	© 2022. The Authors. This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Related URLs:	Google Scholar: Cullen, CL UTAS Profile: Cullen, CL UTAS Profile: Gasperini, R UTAS Profile: Young, KM
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