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

• Published in: Developmental biology 2010-04, Vol.340 (1), p.88-98
• Main Authors: Li, Jin, Kim, Heon, Aceto, Donato G., Hung, Jeffrey, Aono, Shinya, Kemphues, Kenneth J.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Asymmetric division; Atypical protein kinase; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Caenorhabditis elegans Proteins - physiology; Cell polarity; Embryo, Nonmammalian - metabolism; Embryogenesis; Embryonic polarity; Fluorescent Antibody Technique; Ligands; PDZ Domains; Protein Kinase C - genetics; Protein Kinase C - metabolism; Protein-Serine-Threonine Kinases
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2010.01.023

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 βC strand of PAR-6 PDZ binds the βD 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.