CDC-42 regulates PAR protein localization and function to control cellular and embryonic polarity in C. elegans

Background: The polarization of the anterior–posterior axis (A-P) of the Caenorhabditis elegans zygote depends on the activity of the par genes and the presence of intact microfilaments. Functional links between the PAR proteins and the cytoskeleton, however, have not been fully explored. It has recently been shown that in mammalian cells, some PAR homologs form a complex with activated Cdc42, a Rho GTPase that is implicated in the control of actin organization and cellular polarity. A role for Cdc42 in the establishment of embryonic polarity in C. elegans has not been described. Results: To investigate the function of Cdc42 in the control of cellular and embryonic polarity in C. elegans, we used RNA-mediated interference (RNAi) to inhibit cdc-42 activity in the early embryo. Here, we demonstrate that RNAi of cdc-42 disrupts manifestations of polarity in the early embryo, that these phenotypes depend on par-2 and par-3 gene function, and that cdc-42 is required for the localization of the PAR proteins. Conclusions: Our genetic analysis of the regulatory relationships between cdc-42 and the par genes demonstrates that Cdc42 organizes embryonic polarity by controlling the localization and activity of the PAR proteins. Combined with the recent biochemical analysis of their mammalian homologs, these results simultaneously identify both a regulator of the PAR proteins, activated Cdc42, and effectors for Cdc42, the PAR complex.