Page personnelle

Stéphanie MAURIAC




Doctorant

Tél : 33(0)5 57 57 37 81
Envoyer un email



Cursus:
Master 'Biologie Cellulaire Physiologie et Pathologie' Université de Bordeaux (2015)






3 publication(s) depuis Avril 2017:


Trier par

* equal contribution
Les IF indiqués ont été collectés par le Web of Sciences en


21/06/2018 | cell physiol biochem
Galphai Proteins are Indispensable for Hearing.
Beer-Hammer S, Lee SC, Mauriac SA, Leiss V, Groh IAM, Novakovic A, Piekorz RP, Bucher K, Chen C, Ni K, Singer W, Harasztosi C, Schimmang T, Zimmermann U, Pfeffer K, Birnbaumer L, Forge A, Montcouquiol M, Knipper M, Nurnberg B, Ruttiger L

Abstract:
BACKGROUND/AIMS: From invertebrates to mammals, Galphai proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Galphai3-deficiency in pre-hearing murine cochleae pointed to a role of Galphai3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary ('hair') bundle, a requirement for the progression of mature hearing. We found that the lack of Galphai3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound. How these morphological defects translate into hearing phenotypes is not clear. METHODS: Here, we studied global and conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both Galphai proteins. Comparative analyses of global versus Foxg1-driven conditional mutants that mainly delete in the inner ear and telencephalon in combination with functional tests were applied to dissect essential and redundant functions of different Galphai isoforms and to assign specific defects to outer or inner hair cells, the auditory nerve, satellite cells or central auditory neurons. RESULTS: Here we report that lack of Galphai3 but not of the ubiquitously expressed Galphai2 elevates hearing threshold, accompanied by impaired hair bundle elongation and shape in high-frequency cochlear regions. During the crucial reprogramming of the immature inner hair cell (IHC) synapse into a functional sensory synapse of the mature IHC deficiency for Galphai2 or Galphai3 had no impact. In contrast, double-deficiency for Galphai2 and Galphai3 isoforms results in abnormalities along the entire tonotopic axis including profound deafness associated with stereocilia defects. In these mice, postnatal IHC synapse maturation is also impaired. In addition, the analysis of conditional versus global Galphai3-deficient mice revealed that the amplitude of ABR wave IV was disproportionally elevated in comparison to ABR wave I indicating that Galphai3 is selectively involved in generation of neural gain during auditory processing. CONCLUSION: We propose a so far unrecognized complexity of isoform-specific and overlapping Galphai protein functions particular during final differentiation processes.




25/05/2018 | Nat Commun   IF 12.4
Author Correction: Defective Gpsm2/Galphai3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome.
Mauriac SA, Hien YE, Bird JE, Carvalho SD, Peyroutou R, Lee SC, Moreau MM, Blanc JM, Gezer A, Medina C, Thoumine O, Beer-Hammer S, Friedman TB, Ruttiger L, Forge A, Nurnberg B, Sans N, Montcouquiol M

Abstract:
This corrects the article DOI: 10.1038/ncomms14907.




07/04/2017 | Nat Commun   IF 12.4
Defective Gpsm2/Galphai3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome.
Mauriac SA, Hien YE, Bird JE, Carvalho SD, Peyroutou R, Lee SC, Moreau MM, Blanc JM, Geyser A, Medina C, Thoumine O, Beer-Hammer S, Friedman TB, Ruttiger L, Forge A, Nurnberg B*, Sans N*, Montcouquiol M*

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 Galphai3, a well-documented partner of Gpsm2, participates in the elongation process, and its absence also causes hearing deficits. We show that Gpsm2 defines an approximately 200 nm nanodomain at the tips of stereocilia and this localization requires the presence of Galphai3, 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/Galphai3 in the regulation of actin dynamics in epithelial and neuronal tissues.