An instructive role for C. elegans E-cadherin in translating cell contact cues into cortical polarity

Nat Cell Biol. 2015 Jun;17(6):726-35. doi: 10.1038/ncb3168. Epub 2015 May 4.

Abstract

Cell contacts provide spatial cues that polarize early embryos and epithelial cells. The homophilic adhesion protein E-cadherin is required for contact-induced polarity in many cells. However, it is debated whether E-cadherin functions instructively as a spatial cue, or permissively by ensuring adequate adhesion so that cells can sense other contact signals. In Caenorhabditis elegans, contacts polarize early embryonic cells by recruiting the RhoGAP PAC-1 to the adjacent cortex, inducing PAR protein asymmetry. Here we show that the E-cadherin HMR-1, which is dispensable for adhesion, functions together with the α-catenin HMP-1, the p120 catenin JAC-1, and the previously uncharacterized linker PICC-1 (human CCDC85A-C) to bind PAC-1 and recruit it to contacts. Mislocalizing the HMR-1 intracellular domain to contact-free surfaces draws PAC-1 to these sites and depolarizes cells, demonstrating an instructive role for HMR-1 in polarization. Our findings identify an E-cadherin-mediated pathway that translates cell contacts into cortical polarity by directly recruiting a symmetry-breaking factor to the adjacent cortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Catenins / metabolism*
  • Cell Adhesion
  • Cell Polarity
  • Delta Catenin
  • Embryo, Nonmammalian / metabolism
  • Epithelial Cells / metabolism
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism
  • alpha Catenin / metabolism*
  • p120 GTPase Activating Protein / metabolism

Substances

  • Cadherins
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Catenins
  • HMP-1 protein, C elegans
  • JAC-1 protein, C elegans
  • PAC-1 protein, C elegans
  • alpha Catenin
  • hmr-1 protein, C elegans
  • p120 GTPase Activating Protein
  • PAR-1 protein, C elegans
  • Protein Serine-Threonine Kinases
  • Delta Catenin