Willin, an upstream component of the hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts

Moleirinho, S., Patrick, C., Tilston-Lünel, A.M., Higginson, J.R., Angus, L., Antkowiak, M., Barnett, S.C. , Prystowsky, M.B., Reynolds, P.A. and Gunn-Moore, F.J. (2013) Willin, an upstream component of the hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts. PLoS ONE, 8(4), e60028. (doi: 10.1371/journal.pone.0060028) (PMID:23593160) (PMCID:PMC3620498)

[img]
Preview
Text
80688.pdf - Published Version
Available under License Creative Commons Attribution.

6MB

Abstract

Willin/FRMD6 was first identified in the rat sciatic nerve, which is composed of neurons, Schwann cells, and fibroblasts. Willin is an upstream component of the Hippo signaling pathway, which results in the inactivation of the transcriptional co-activator YAP through Ser127 phosphorylation. This in turn suppresses the expression of genes involved in cell growth, proliferation and cancer development ensuring the control of organ size, cell contact inhibition and apoptosis. Here we show that in the mammalian sciatic nerve, Willin is predominantly expressed in fibroblasts and that Willin expression activates the Hippo signaling cascade and induces YAP translocation from the nucleus to the cytoplasm. In addition within these cells, although it inhibits cellular proliferation, Willin expression induces a quicker directional migration towards scratch closure and an increased expression of factors linked to nerve regeneration. These results show that Willin modulates sciatic nerve fibroblast activity indicating that Willin may have a potential role in the regeneration of the peripheral nervous system.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Higginson, Dr Jennifer and Barnett, Professor Susan
Authors: Moleirinho, S., Patrick, C., Tilston-Lünel, A.M., Higginson, J.R., Angus, L., Antkowiak, M., Barnett, S.C., Prystowsky, M.B., Reynolds, P.A., and Gunn-Moore, F.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS ONE 8(4):e60028
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record