Vangl2 is one of the central proteins controlling the establishment of planar cell polarity in multiple tissues of different species. Previous studies suggest that the localization of the Vangl2 protein to specific intracellular microdomains is crucial for its function. However, the molecular mechanisms that control Vangl2 trafficking within a cell are largely unknown. Here, we identify Gipc1 (GAIP C-terminus interacting protein 1) as a new interactor for Vangl2, and we show that a myosin VI-Gipc1 protein complex can regulate Vangl2 traffic in heterologous cells. Furthermore, we show that in the cochlea of MyoVI mutant mice, Vangl2 presence at the membrane is increased, and that a disruption of Gipc1 function in hair cells leads to maturation defects, including defects in hair bundle orientation and integrity. Finally, stimulated emission depletion microscopy and overexpression of GFP-Vangl2 show an enrichment of Vangl2 on the supporting cell side, adjacent to the proximal membrane of hair cells. Altogether, these results indicate a broad role for Gipc1 in the development of both stereociliary bundles and cell polarization, and suggest that the strong asymmetry of Vangl2 observed in early postnatal cochlear epithelium is mostly a ‘tissue’ polarity readout.< Réduire

Mots clés en anglais

Polarity

Traffic

Actin

Cochlea

Van Gogh-like 2

Gipc1

Myosin VI

Planar polarity

Mouse

Rat

URI

https://oskar-bordeaux.fr/handle/20.500.12278/140345

DOI

http://dx.doi.org/10.1242/dev.074229

Project ANR

Caractérisation moléculaire et fonctionnelle de vangl2 et de ses partenaires chez le mammifère - ANR-08-MNPS-0040
Caractérisations moléculaire et fonctionnelle de la protéine Scribble 1 au cours du développement du système nerveux central - ANR-07-NEUR-0031

Unités de recherche

Neurocentre Magendie - U1215

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Gipc1 has a dual role in Vangl2 trafficking and hair bundle integrity in the inner ear

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