title: Rho-binding kinase (LET-502) and myosin phosphatase (MEL-11) regulate cytokinesis in the early Caenorhabditis elegans embryo.
abstract: Rho-binding kinase and myosin phosphatase regulate the contraction of actomyosin filaments in non-muscle and smooth muscle cells. Previously, we described the role of C. elegans genes encoding Rho-binding kinase (let-502) and myosin phosphatase targeting subunit (mel-11) in epidermal cell-shape changes that drive morphogenesis and in spermathecal contraction. Here we analyze their roles in a third contractile event, cytokinesis within early embryos. We demonstrate that these genes function together to regulate the rate of cleavage furrow contraction, with Rho-binding kinase/LET-502 mediating contraction, whereas myosin phosphatase/MEL-11 acts as a brake to contraction: early embryonic cleavage often fails or is slowed when let-502 is mutated, whereas mel-11 mutations result in ectopic furrowing and faster furrow ingression. These phenotypes correspond to changes in the levels of phosphorylated regulatory non-muscle myosin light chain (rMLC). The gene products of let-502 and mel-11 colocalize at cleavage furrows, and their mutations alleviate one another's defects. rMLC is phosphorylated in let-502; mel-11 double mutants, indicating that a kinase is able to phosphorylate rMLC in the absence of both LET-502 and MEL-11. Genetic and molecular epistasis experiments place LET-502 and MEL-11 in a cytokinetic pathway. LET-502 and MEL-11 regulate the activity of non-muscle myosin after actin, non-muscle myosin heavy chain/NMY-2, regulatory non-muscle myosin light chain/MLC-4 and early formin/CYK-1 have formed a contractile ring. Proteins including Rho GTPase activating protein/CYK-4 and late CYK-1, which are required for late stages of cytokinesis, function downstream of LET-502 and MEL-11.
authors: Genes and Development Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1.
authors: Alisa J
authors: AJ
authors: Piekny
authors: Paul E
authors: PE
authors: Mains
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins; D002455:Cell Division / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D015801:Helminth Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation / Q000235:genetics; D018995:Myosin Heavy Chains / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D054460:rho-Associated Kinases
chemical_list: D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; C114201:cyk-1 protein, C elegans; C515856:LET-502 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D010749:Phosphoprotein Phosphatases; D043263:Myosin-Light-Chain Phosphatase; D018995:Myosin Heavy Chains