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

Arnaud P. Giese, Jérome Ezan, Lingyan Wang, Léa Lasvaux, Frédérique Lembo, Claire Mazzocco, Elodie Richard, Jérome Reboul, Jean Paul Borg, Matthew W. Kelley, Nathalie Sans, John Brigande, Mireille Montcouquiol

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3775-3785
Number of pages11
JournalDevelopment (Cambridge)
Volume139
Issue number20
DOIs
StatePublished - Oct 15 2012

    Fingerprint

Keywords

  • Actin
  • Cochlea
  • Gipc1
  • Mouse
  • Myosin VI
  • Planar polarity
  • Polarity
  • Rat
  • Traffic
  • Van gogh-like 2

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Giese, A. P., Ezan, J., Wang, L., Lasvaux, L., Lembo, F., Mazzocco, C., Richard, E., Reboul, J., Borg, J. P., Kelley, M. W., Sans, N., Brigande, J., & Montcouquiol, M. (2012). Gipc1 has a dual role in Vangl2 trafficking and hair bundle integrity in the inner ear. Development (Cambridge), 139(20), 3775-3785. https://doi.org/10.1242/dev.074229