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.

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

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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.< Leer menos

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

DOI

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

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Développment d'une infrastructure française distribuée coordonnée
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043
Pathophysiologie du complexe Gai/mPins dans l'oreille interne

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Neurocentre Magendie - U1215

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

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