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Protocadherin 15 suppresses oligodendrocyte progenitor cell proliferation and promotes motility through distinct signalling pathways

Citation

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, Protocadherin 15 suppresses oligodendrocyte progenitor cell proliferation and promotes motility through distinct signalling pathways, Communications Biology, 5 pp. 511. ISSN 2399-3642 (2022) [Refereed Article]


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DOI: doi:10.1038/s42003-022-03470-1

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 Details

Item Type:Refereed Article
Keywords:protocadherin 15, oligodendrocyte progenitor cell, glioma, proliferation, cytoskeleton
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Zhen, Y (Miss Yilan Zhen)
UTAS Author:Cullen, CL (Dr Carlie Cullen)
UTAS Author:Ricci, R (Mr Raphael Ricci)
UTAS Author:Summers, BS (Mr Benjamin Summers)
UTAS Author:Gasperini, R (Dr Rob Gasperini)
UTAS Author:Young, KM (Associate Professor Kaylene Young)
ID Code:150188
Year Published:2022
Funding Support:Australian Research Council (DP180101494)
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-06-01
Last Modified:2022-06-01
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