Mahuzier, A., Gaudé, H.M., Grampa, V., Anselme, I., Silbermann, F., Leroux-Berger, M., Delacour, D., Ezan, J., Montcouquiol, M., Saunier, S., Schneider-Maunoury, S., and Vesque, C. (2012) Dishevelled stabilization by the ciliopathy protein Rpgrip1l is essential for planar cell polarity. The Journal of cell biology. 198(5):927-940.
Cilia are at the core of planar polarity cellular events in many systems. However, the molecular mechanisms by which they
influence the polarization process are unclear. Here, we identify the function of the ciliopathy protein Rpgrip1l in planar
polarity. In the mouse cochlea and in the zebrafish floor plate, Rpgrip1l was required for positioning the basal body along
the planar polarity axis. Rpgrip1l was also essential for stabilizing dishevelled at the cilium base in the zebrafish floor
plate and in mammalian renal cells. In rescue experiments, we showed that in the zebrafish floor plate the function of Rpgrip1l
in planar polarity was mediated by dishevelled stabilization. In cultured cells, Rpgrip1l participated in a complex with inversin
and nephrocystin-4, two ciliopathy proteins known to target dishevelled to the proteasome, and, in this complex, Rpgrip1l
prevented dishevelled degradation. We thus uncover a ciliopathy protein complex that finely tunes dishevelled levels, thereby
modulating planar cell polarity processes.