title: Gipc1 has a dual role in Vangl2 trafficking and hair bundle integrity in the inner ear.
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.
authors.affiliation: Planar Polarity and Plasticity Group, Inserm U862, Neurocentre Magendie, Bordeaux,  France.
authors.forename: Arnaud P
authors.initials: AP
authors.lastname: Giese
authors.forename: Jérome
authors.initials: J
authors.lastname: Ezan
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.forename: Léa
authors.initials: L
authors.lastname: Lasvaux
authors.forename: Frédérique
authors.initials: F
authors.lastname: Lembo
authors.forename: Claire
authors.initials: C
authors.lastname: Mazzocco
authors.forename: Elodie
authors.initials: E
authors.lastname: Richard
authors.forename: Jérome
authors.initials: J
authors.lastname: Reboul
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Borg
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kelley
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sans
authors.forename: John
authors.initials: J
authors.lastname: Brigande
authors.forename: Mireille
authors.initials: M
authors.lastname: Montcouquiol
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D007758:Ear, Inner / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D057809:HEK293 Cells; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018995:Myosin Heavy Chains / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C115271:Gipc1 protein, mouse; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D034741:RNA, Small Interfering; C089785:myosin VI; D049452:Green Fluorescent Proteins; D018995:Myosin Heavy Chains