MAURIAC, Stephanie A.; HIEN, Yeri E.; BIRD, Jonathan E.; DOS SANTOS CARVALHO, Steve; PEYROUTOU, Ronan; LEE, Sze Chim; MOREAU, Maite M.; BLANC, Jean-Michel; GEZER, Aysegul; MEDINA, Chantal; THOUMINE, Olivier; BEER-HAMMER, Sandra; FRIEDMAN, Thomas B.; RUTTIGER, Lukas; FORGE, Andrew; NURNBERG, Bernd; SANS, Nathalie; MONTCOUQUIOL, Mireille

doi:10.1038/ncomms14907

MAURIAC, Stephanie A.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

HIEN, Yeri E.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

BIRD, Jonathan E.

Langue

Article de revue

Ce document a été publié dans

Nature Communications. 2017-04-07, vol. 8, p. 14907

Résumé en anglais

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.< Réduire

URI

https://oskar-bordeaux.fr/handle/20.500.12278/140504

DOI

http://dx.doi.org/10.1038/ncomms14907

Project ANR

Développment d'une infrastructure française distribuée coordonnée - ANR-10-INBS-0004
Bordeaux Region Aquitaine Initiative for Neuroscience
Pathophysiologie du complexe Gai/mPins dans l'oreille interne - ANR-14-CE13-0013

Unités de recherche

Neurocentre Magendie - U1215

Voir/Ouvrir

Métadonnées

Partager cette publication !

Licence d’utilisation du document

Defective Gpsm2/Gαi3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome

Langue

Ce document a été publié dans

Résumé en anglais

URI

DOI

Project ANR

Unités de recherche