title: Depletion of the co-chaperone CDC-37 reveals two modes of PAR-6 cortical association in C. elegans embryos.
abstract: PAR proteins play roles in the establishment and maintenance of polarity in many different cell types in metazoans. In C. elegans, polarity established in the one-cell embryo determines the anteroposterior axis of the developing animal and is essential to set the identities of the early blastomeres. PAR-1 and PAR-2 colocalize at the posterior cortex of the embryo. PAR-3, PAR-6 and PKC-3 (aPKC) colocalize at the anterior cortex of the embryo. A process of mutual exclusion maintains the anterior and posterior protein domains. We present results indicating that a homolog of the Hsp90 co-chaperone Cdc37 plays a role in dynamic interactions among the PAR proteins. We show that CDC-37 is required for the establishment phase of embryonic polarity; that CDC-37 reduction allows PAR-3-independent cortical accumulation of PAR-6 and PKC-3; and that CDC-37 is required for the mutual exclusion of the anterior and posterior group PAR proteins. Our results indicate that CDC-37 acts in part by maintaining PKC-3 levels and in part by influencing the activity or levels of other client proteins. Loss of the activities of these client proteins reveals that there are two sites for PAR-6 cortical association, one dependent on CDC-42 and not associated with PAR-3, and the other independent of CDC-42 and co-localizing with PAR-3. We propose that, in wild-type embryos, CDC-37-mediated inhibition of the CDC-42-dependent binding site and PAR-3-mediated release of this inhibition provide a key mechanism for the anterior accumulation of PAR-6.
authors.affiliation: Department of Molecular Biology and Genetics, 101 Biotechnology Building, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Beers
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kemphues
mesh_terms: D000818:Animals; D001665:Binding Sites; D019521:Body Patterning / Q000235:genetics; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D003593:Cytoplasm / Q000737:chemistry; D004625:Embryo, Nonmammalian / Q000737:chemistry / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D018832:Molecular Chaperones / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000032:analysis / Q000378:metabolism; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D034622:RNA Interference; D008941:Spindle Apparatus / Q000737:chemistry
chemical_list: C515008:CDC-37 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; C480837:NMY-2 protein, C elegans; C081779:cdc-42 protein, C elegans; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D018995:Myosin Heavy Chains