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

Dev Cell. 2017 Aug 21;42(4):400-415.e9. doi: 10.1016/j.devcel.2017.07.007. Epub 2017 Aug 3.

Abstract

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.

Keywords: CDC-42; PAR clusters; PAR proteins; PAR-3; PAR-6; PKC-3; actomyosin flow; atypical protein kinase C; cell polarity; symmetry breaking.

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Polarity*
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Zygote / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • cdc-42 protein, C elegans
  • par-6 protein, C elegans
  • PAR-3 protein, C elegans
  • Protein Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • GTP-Binding Proteins