TY - JOUR
T1 - Protocadherin 15 suppresses oligodendrocyte progenitor cell proliferation and promotes motility through distinct signalling pathways
AU - Zhen, Yilan
AU - Cullen, Carlie L.
AU - Ricci, Raphael
AU - Summers, Benjamin S.
AU - Rehman, Sakina
AU - Ahmed, Zubair M.
AU - Foster, Antoinette Y.
AU - Emery, Ben
AU - Gasperini, Robert
AU - Young, Kaylene M.
N1 - Funding Information:
We thank our colleagues at the University of Tasmania for constructive feedback and suggestions for improvement. We thank Dominic Cosgrove for providing the rabbit anti-Pcdh15 antibody for immunocytochemistry (Boys Town National Research Hospital, Boys Town, United States of America, NE 68010). This research was supported by grants from the National Health and Medical Research Council of Australia (NHMRC: 1077792, 1139041), the Medical Research Future Fund (EPCD00008), MS Research Australia (11-014, 16-105, 17-007), the National Institute of Health (1R21NS111211-01A1, R01DC016295) and the Australian Research Council (DP180101494). Y.Z. was supported by scholarships from the Menzies Institute for Medical Research at the University of Tasmania and Anhui Medical University. B.S.S. was supported by a scholarship from Dementia Australia (K0025637). B.E. was supported by an endowment from the Warren family. A.Y.F. was supported by a Howard Hughes Medical Institute Gilliam Fellowship. C.L.C. was supported by a fellowship from MS Research Australia and the Penn Foundation (15-054). K.M.Y. was supported by a Paired Fellowship from MS Research Australia and the Macquarie Group Foundation (17-0223) and a Senior Research Fellowship from MS Australia (21-3023). The funding sources had no role in the study design; collection, analysis or interpretation of the data; writing the manuscript, or the publication process.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85130976301&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85130976301&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-03470-1
DO - 10.1038/s42003-022-03470-1
M3 - Article
C2 - 35637313
AN - SCOPUS:85130976301
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 511
ER -