UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Defective Gpsm2/G alpha(i3) signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome

Mauriac, SA; Hien, YE; Bird, JE; Carvalho, SD-S; Peyroutou, R; Lee, SC; Moreau, MM; ... Montcouquiol, M; + view all (2017) Defective Gpsm2/G alpha(i3) signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome. Nature Communications , 8 , Article 14907. 10.1038/ncomms14907. Green open access

[thumbnail of Bracey_ncomms14907.pdf]
Preview
Text
Bracey_ncomms14907.pdf - Published Version

Download (5MB) | Preview

Abstract

Mutations in GPSM2 cause Chudley-McCullough syndrome (CMCS), an autosomal recessive neurological disorder characterized by early-onset sensorineural deafness and brain anomalies. Here, we show that mutation of the mouse orthologue of GPSM2 affects actin-rich stereocilia elongation in auditory and vestibular hair cells, causing deafness and balance defects. The G-protein subunit Gαi3, a well-documented partner of Gpsm2, participates in the elongation process, and its absence also causes hearing deficits. We show that Gpsm2 defines an ∼200 nm nanodomain at the tips of stereocilia and this localization requires the presence of Gαi3, myosin 15 and whirlin. Using single-molecule tracking, we report that loss of Gpsm2 leads to decreased outgrowth and a disruption of actin dynamics in neuronal growth cones. Our results elucidate the aetiology of CMCS and highlight a new molecular role for Gpsm2/Gαi3 in the regulation of actin dynamics in epithelial and neuronal tissues.

Type: Article
Title: Defective Gpsm2/G alpha(i3) signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms14907
Publisher version: http://dx.doi.org/10.1038/ncomms14907
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, Hair-Cell Stereocilia, Hearing-Loss, Unconventional Myosin, Inner-Ear, Spindle Orientation, Deafness Dfnb3, Protein, Whirlin, Elongation, Mouse
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
URI: https://discovery.ucl.ac.uk/id/eprint/1553033
Downloads since deposit
26Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item