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

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Gunn_Moore_pone0060028Willin.pdf (5.735Mb)
Date
08/04/2013
Author
Moleirinho, Susan
Patrick, Calum
Tilston-Lunel, Andrew Martin
Higginson, JR
Angus, Liselotte
Antkowiak, Maciej
Barnett, Susan
Prystowsky, Michael
Reynolds, Paul Andrew
Gunn-Moore, Frank J
Keywords
QP Physiology
SDG 3 - Good Health and Well-being
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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 coactivator 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.
Citation
Moleirinho , S , Patrick , C , Tilston-Lunel , A M , Higginson , JR , Angus , L , Antkowiak , M , Barnett , S , Prystowsky , M , Reynolds , P A & Gunn-Moore , F J 2013 , ' Willin, an upstream component of the Hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts ' , PLoS ONE , vol. 8 , no. 4 , e60028 . https://doi.org/10.1371/journal.pone.0060028
Publication
PLoS ONE
Status
Peer reviewed
DOI
https://doi.org/10.1371/journal.pone.0060028
ISSN
1932-6203
Type
Journal article
Rights
© 2013 Moleirinho et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/3474

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