Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit

Nat Chem Biol. 2018 Oct;14(10):917-927. doi: 10.1038/s41589-018-0117-1. Epub 2018 Sep 3.

Abstract

Cell polarity is the asymmetric compartmentalization of cellular components. An opposing gradient of partitioning-defective protein kinases, atypical protein kinase C (aPKC) and PAR-1, at the cell cortex guides diverse asymmetries in the structure of metazoan cells, but the mechanism underlying their spatial patterning remains poorly understood. Here, we show in Caenorhabditis elegans zygotes that the cortical PAR-1 gradient is patterned as a consequence of dual mechanisms: stabilization of cortical dynamics and protection from aPKC-mediated cortical exclusion. Dual control of cortical PAR-1 depends on a physical interaction with the PRBH-domain protein PAR-2. Using a reconstitution approach in heterologous cells, we demonstrate that PAR-1, PAR-2, and polarized Cdc42-PAR-6-aPKC comprise the minimal network sufficient for the establishment of an opposing cortical gradient. Our findings delineate the mechanism governing cortical polarity, in which a circuit consisting of aPKC and the PRBH-domain protein ensures the local recruitment of PAR-1 to a well-defined cortical compartment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Polarity
  • Green Fluorescent Proteins / metabolism
  • Lipids / chemistry
  • Mutagenesis
  • Phosphorylation
  • Protein Binding
  • Protein Domains
  • Protein Interaction Mapping
  • Protein Kinase C / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference

Substances

  • Caenorhabditis elegans Proteins
  • Lipids
  • par-2 protein, C elegans
  • Green Fluorescent Proteins
  • PAR-1 protein, C elegans
  • Protein-Serine-Threonine Kinases
  • Protein Kinase C