aPKC cycles between functionally distinct PAR protein assemblies to drive cell polarity
journal contributionposted on 2020-10-14, 13:15 authored by Josana Rodriguez, Florent Peglion, Jack Martin, Lars Hubatsch, Jacob Reich, Nisha Hirani, Alicia G Gubieda, Jon Roffey, Artur Ribeiro Fernandes, Daniel St Johnston, Julie Ahringer, Nathan W Goehring
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.
CDC-42PAR clustersPAR proteinsPAR-3PAR-6PKC-3actomyosin flowatypical protein kinase Ccell polaritysymmetry breakingAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsCell Cycle ProteinsCell PolarityCyclic AMP-Dependent Protein KinasesGTP-Binding ProteinsHEK293 CellsHumansProtein BindingProtein-Serine-Threonine KinasesZygoteGoehring FC00108606 Biological Sciences11 Medical and Health SciencesDevelopmental Biology