Feedback mechanisms between PAR polarity effectors and the actomyosin cytoskeleton

Abstract

The Caenorhabditis elegans zygote is polarised into an anterior and a posterior domain thanks to PAR proteins and the actomyosin cytoskeleton. These proteins are well conserved and play a central role in polarising different animal cell types. In the C. elegans zygote cortex, the actomyosin cytoskeleton organises into ‘foci’ structures, which depend on the RHO-1/ LET-502 pathway (orthologues of the human RHO-A and ROCK) and polarise the PAR proteins thanks to actomyosin flow. Although this process has been well described, very little is known so far about how PAR proteins could in turn regulate the actomyosin cytoskeleton. In the anterior domain, PAR proteins organise in two distinct complexes: a PAR-3 dependent complex, and the CDC-42 dependent complex. The kinase PKC-3 can bind both, and is active when bound to CDC-42. In this thesis we explore the dynamics of the CDC-42/PKC-3 complex and identify PKC-3 as a positive regulator the actomyosin flow via regulation of the RHO/LET-502 pathway, and via phoshoryation of CDC-42. Furthermore, we identify two feedback mechanisms between LET-502 and anterior PARs: LET-502 can regulate the organisation of anterior PARs and is required for recruitment of phosphorylated CDC-42 to actomyosin foci.