Primary cilium migration depends on G-protein signalling control of subapical cytoskeleton.
In ciliated mammalian cells, the precise migration of the primary cilium at the apical surface of the cells, also referred to as translational polarity, defines planar cell polarity (PCP) in very early stages. Recent research has revealed a co-dependence between planar polarization of some cell types and cilium positioning at the surface of cells. This important role of the primary cilium in mammalian cells is in contrast with its absence from Drosophila melanogaster PCP establishment. Here, we show that deletion of GTP-binding protein alpha-i subunit 3 (Gαi3) and mammalian Partner of inscuteable (mPins) disrupts the migration of the kinocilium at the surface of cochlear hair cells and affects hair bundle orientation and shape. Inhibition of G-protein function in vitro leads to kinocilium migration defects, PCP phenotype and abnormal hair bundle morphology. We show that Gαi3/mPins are expressed in an apical and distal asymmetrical domain, which is opposite and complementary to an aPKC/Par-3/Par-6b expression domain, and non-overlapping with the core PCP protein Vangl2. Thus G-protein-dependent signalling controls the migration of the cilium cell autonomously, whereas core PCP signalling controls long-range tissue PCP.
1] INSERM, Planar Polarity and Plasticity Group, Neurocentre Magendie, 33077 Bordeaux, France [2] Université Bordeaux, Neurocentre Magendie, Bordeaux 33077, France.
Jerome
J
Ezan
Léa
L
Lasvaux
Aysegul
A
Gezer
Ana
A
Novakovic
Helen
H
May-Simera
Edwige
E
Belotti
Anne-Catherine
AC
Lhoumeau
Lutz
L
Birnbaumer
Sandra
S
Beer-Hammer
Jean-Paul
JP
Borg
André
A
Le Bivic
Bernd
B
Nürnberg
Nathalie
N
Sans
Mireille
M
Montcouquiol
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002465:Cell Movement; D016764:Cell Polarity; D048430:Cell Shape; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C502655:LGN protein, mouse; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; C518597:Par6 protein, mouse; C115084:Pard3 protein, mouse; C115015:PKC-3 protein; D011493:Protein Kinase C; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C417708:Gnai3 protein, mouse