Rho and polarity establishment

CYK-4/GAP Provides a Localized Cue to Initiate Anteroposterior Polarity upon Fertilization
Noah Jenkins, Jennifer R. Saam, and Susan E. Mango
Published online 27 July 2006, Science
[DOI: 10.1126/science.1130291]

Establishment of Cell Polarity is key in several cellular contexts. Small GTPases, in particular Cdc42, are known regulators of cell polarity. It was known from previous works that the sperm determines the posterior pole of the C. elegans embryo. Righ after fertilization, during pronuclear migration, a wave of cortical actin (cortical actin flow) and myosin II moves away from the site of sperm entry, which becomes the posterior pole, and is involved in polarization of PAR-3 and -6 to the anterior pole, and PAR-2 to the posterior.

The identity of the sperm protein responsible for setting the cue remained unanswered until now. Schonegg et al. identified a RHO-GAP (CYK-4) that is required for the establishment of polarity. CYK-4 is present in the sperm centrosome and no actin or myosin polarization is observed in the absence of paternal CYK-4. CYK-4 is a GAP for RHO, i.e. it inhibits RHO activation. The authors propose that CYK-4 breaks down the symmetry in the actin cytoskeleton, resulting in cortical actin flow away from sperm entry site.

So how does Rho regulates actin cytoskeleton? The obvious candidate is Rho Kinase (ROCK), which activates myosin II and originates actin bundling. So a model can be proposed where local inhibition of Rho by CYK-4, leads to inhibition of ROCK and myosin II at the future posterior pole. The C. elegans homologue of ROCK is Let-502 and it is not know to be involved in the establishment of C. elegans embryo polarity, so probably we will soon find out...