title: Willin, an upstream component of the hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts.
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.
authors.affiliation: Medical and Biological Sciences Building, School of Medicine, University of St Andrews, St Andrews, United Kingdom.
authors.forename: Susana
authors.initials: S
authors.lastname: Moleirinho
authors.forename: Calum
authors.initials: C
authors.lastname: Patrick
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tilston-Lünel
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Higginson
authors.forename: Liselotte
authors.initials: L
authors.lastname: Angus
authors.forename: Maciej
authors.initials: M
authors.lastname: Antkowiak
authors.forename: Susan C
authors.initials: SC
authors.lastname: Barnett
authors.forename: Michael B
authors.initials: MB
authors.lastname: Prystowsky
authors.forename: Paul A
authors.initials: PA
authors.lastname: Reynolds
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gunn-Moore
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D002465:Cell Movement; D049109:Cell Proliferation; D036388:Ephrin-B2 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D000090683:Hippo Signaling Pathway; D006706:Homeostasis; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology*; D015398:Signal Transduction; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D036388:Ephrin-B2; C574382:Frmd6 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases