PAR proteins direct asymmetry of the cell cycle regulators Polo-like kinase and Cdc25.
Cell cycle lengths vary widely among different cells within an animal, yet mechanisms of cell cycle length regulation are poorly understood. In the Caenorhabditis elegans embryo, the first cell division produces two cells with different cell cycle lengths, which are dependent on the conserved partitioning-defective (PAR) polarity proteins. We show that two key cell cycle regulators, the Polo-like kinase PLK-1 and the cyclin-dependent kinase phosphatase CDC-25.1, are asymmetrically distributed in early embryos. PLK-1 shows anterior cytoplasmic enrichment and CDC-25.1 shows PLK-1-dependent enrichment in the anterior nucleus. Both proteins are required for normal mitotic progression. Furthermore, these asymmetries are controlled by PAR proteins and the muscle excess (MEX) proteins MEX-5/MEX-6, and the latter is linked to protein degradation. Our results support a model whereby the PAR and MEX-5/MEX-6 proteins asymmetrically control PLK-1 levels, which asymmetrically regulates CDC-25.1 to promote differences in cell cycle lengths. We suggest that control of Plk1 and Cdc25 may be relevant to regulation of cell cycle length in other developmental contexts.
Rivers
David M
DM
The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB2 1QN, England, UK.
Moreno
Sergio
S
Abraham
Mary
M
Ahringer
Julie
J
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D016764:Cell Polarity / Q000235:genetics; D048749:Cytokinesis / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020666:ras-GRF1 / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D020666:ras-GRF1; C410587:MEX-5 protein, C elegans; C410589:MEX-6 protein, C elegans; C512642:par-6 protein, C elegans; C513017:plk-1 protein, C elegans; D000097869:Polo-Like Kinase 1