PP1 phosphatases control PAR-2 localization and polarity establishment in C. elegans embryos

Abstract

Cell polarity relies on the asymmetric distribution of the conserved PAR proteins, which is regulated by phosphorylation/dephosphorylation reactions. While the kinases involved have been well studied, the role of phosphatases remains poorly understood. In C. elegans zygotes, phosphorylation of the posterior PAR-2 protein by the atypical protein kinase PKC-3 inhibits PAR-2 cortical localization. Polarity establishment depends on loading of PAR-2 at the posterior cortex. We show that the PP1 phosphatases GSP-1 and GSP-2 are required for polarity establishment in embryos. We find that co-depletion of GSP-1 and GSP-2 abrogates the cortical localization of PAR-2 and that GSP-1 and GSP-2 interact with PAR-2 via a PP1 docking motif in PAR-2. Mutating this motif in vivo, to prevent binding of PAR-2 to PP1, abolishes cortical localization of PAR-2, while optimizing this motif extends PAR-2 cortical localization. Our data suggest a model in which GSP-1/-2 counteract PKC-3 phosphorylation of PAR-2 allowing its cortical localization at the posterior and polarization of the one-cell embryo. SUMMARYCalvi et al. identify PP1 protein phosphatases as regulators of cell polarity in C. elegans embryos. Their results show that two redundant phosphatases, GSP-1 and GSP-2, interact with the polarity protein PAR-2 and control its localization and polarity establishment.