CDC-42 controls early cell polarity and spindle orientation in C. elegans.
BACKGROUND
Generation of asymmetry in the one-cell embryo of C. elegans establishes the anterior--posterior axis (A-P), and is necessary for the proper identity of early blastomeres. Conserved PAR proteins are asymmetrically distributed and are required for the generation of this early asymmetry. The small G protein Cdc42 is a key regulator of polarity in other systems, and recently it has been shown to interact with the mammalian homolog of PAR-6. The function of Cdc42 in C. elegans had not yet been investigated, however.


RESULTS
Here, we show that C. elegans cdc-42 plays an essential role in the polarity of the one-cell embryo and the proper localization of PAR proteins. Inhibition of cdc-42 using RNA interference results in embryos with a phenotype that is nearly identical to par-3, par-6, and pkc-3 mutants, and asymmetric localization of these and other PAR proteins is lost. We further show that C. elegans CDC-42 physically interacts with PAR-6 in a yeast two-hybrid system, consistent with data on the interaction of human homologs.


CONCLUSIONS
Our results show that CDC-42 acts in concert with the PAR proteins to control the polarity of the C. elegans embryo, and provide evidence that the interaction of CDC-42 and the PAR-3/PAR-6/PKC-3 complex has been evolutionarily conserved as a functional unit.
Gotta
M
M
Wellcome/CRC Institute, Tennis Court Road, Cambridge CB2 1QR, UK.
Abraham
M C
MC
Ahringer
J
J
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000196:embryology* / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D018510:RNA, Helminth / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D008941:Spindle Apparatus / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D015801:Helminth Proteins; D011506:Proteins; D018510:RNA, Helminth; C081779:cdc-42 protein, C elegans; C512642:par-6 protein, C elegans; C115015:PKC-3 protein; D011493:Protein Kinase C; D019204:GTP-Binding Proteins