aPKC Cycles between Functionally Distinct PAR Protein Assemblies to Drive Cell Polarity

The conserved polarity effector proteins PAR-3, PAR-6, CDC-42, and atypical protein kinase C (aPKC) form a core unit of the PAR protein network, which plays a central role in polarizing a broad range of animal cell types. To functionally polarize cells, these proteins must activate aPKC within a spatially defined membrane domain on one side of the cell in response to symmetry-breaking cues. Using the Caenorhabditis elegans zygote as a model, we find that the localization and activation of aPKC involve distinct, specialized aPKC-containing assemblies: a PAR-3-dependent assembly that responds to polarity cues and promotes efficient segregation of aPKC toward the anterior but holds aPKC in an inactive state, and a CDC-42-dependent assembly in which aPKC is active but poorly segregated. Cycling of aPKC between these distinct functional assemblies, which appears to depend on aPKC activity, effectively links cue-sensing and effector roles within the PAR network to ensure robust establishment of polarity.This work was supported by a Faculty Fellowship from Newcastle University and a Royal Society Research Grant (RG2015R2 to J. Rodriguez), a BBSRC PhD fellowship (J.M.), a PhD fellowship from Newcastle University (A.G.G.), Wellcome Trust Senior and Principal Research Fellowships (054523, to J.A.; 080007, to D.StJ.), a University of Cambridge Studentship via the Wellcome Trust PhD Program in Developmental Biology (A.R.F.), and the Francis Crick Institute (N.W.G.), which receives its core funding from Cancer Research UK (FC001086), the UK Medical Research Council (FC001086), and the Wellcome Trust (FC001086). N.W.G. and J. Rodriguez are members of the GENiE network supported by COST Action BM1408 and EMBO