Binding to PKC-3, but not to PAR-3 or to a conventional PDZ domain ligand, is required for PAR-6 function in C. elegans

Dev Biol. 2010 Apr 1;340(1):88-98. doi: 10.1016/j.ydbio.2010.01.023. Epub 2010 Feb 1.

Abstract

PAR-6 is a conserved protein important for establishment and maintenance of cell polarity in a variety of metazoans. PAR-6 proteins function together with PAR-3, aPKC and CDC-42. Mechanistic details of their interactions, however, are not fully understood. We studied the biochemical interactions between C. elegans PAR-6 and its binding partners and tested the requirements of these interactions in living worms. We show that PB1 domain-mediated binding of PAR-6 to PKC-3 is necessary for polarity establishment and PAR-6 cortical localization in C. elegans embryos. We also show that binding of PAR-6 and PAR-3 is mediated in vitro by a novel type of PDZ-PDZ interaction; the betaC strand of PAR-6 PDZ binds the betaD strand of PAR-3 PDZ1. However, this interaction is dispensable in vivo for PAR-6 function throughout the life of C. elegans. Mutations that specifically abolish conventional ligand binding to the PAR-6 PDZ domain also failed to affect PAR-6 function in vivo. We conclude that PAR-6 binding to PKC-3, but not to PAR-3 nor to a conventional PDZ ligand, is required for PAR-6 cortical localization and function in C. elegans.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology*
  • Embryo, Nonmammalian / metabolism
  • Fluorescent Antibody Technique
  • Ligands
  • PDZ Domains*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein-Serine-Threonine Kinases

Substances

  • Caenorhabditis elegans Proteins
  • Ligands
  • par-6 protein, C elegans
  • PAR-3 protein, C elegans
  • Protein-Serine-Threonine Kinases
  • PKC-3 protein
  • Protein Kinase C