Coordination of Recombination with Meiotic Progression in the Caenorhabditis elegans Germline by KIN-18, a TAO Kinase That Regulates the Timing of MPK-1 Signaling.
Meiosis is a tightly regulated process requiring coordination of diverse events. A conserved ERK/MAPK-signaling cascade plays an essential role in the regulation of meiotic progression. The Thousand And One kinase (TAO) kinase is a MAPK kinase kinase, the meiotic role of which is unknown. We have analyzed the meiotic functions of KIN-18, the homolog of mammalian TAO kinases, in Caenorhabditis elegans. We found that KIN-18 is essential for normal meiotic progression; mutants exhibit accelerated meiotic recombination as detected both by analysis of recombination intermediates and by crossover outcome. In addition, ectopic germ-cell differentiation and enhanced levels of apoptosis were observed in kin-18 mutants. These defects correlate with ectopic activation of MPK-1 that includes premature, missing, and reoccurring MPK-1 activation. Late progression defects in kin-18 mutants are suppressed by inhibiting an upstream activator of MPK-1 signaling, KSR-2. However, the acceleration of recombination events observed in kin-18 mutants is largely MPK-1-independent. Our data suggest that KIN-18 coordinates meiotic progression by modulating the timing of MPK-1 activation and the progression of recombination events. The regulation of the timing of MPK-1 activation ensures the proper timing of apoptosis and is required for the formation of functional oocytes. Meiosis is a conserved process; thus, revealing that KIN-18 is a novel regulator of meiotic progression in C. elegans would help to elucidate TAO kinase's role in germline development in higher eukaryotes.
Department of Biology, University of Iowa, Iowa City, Iowa 52242.
Yizhi
Y
Yin
Department of Biology, University of Iowa, Iowa City, Iowa 52242.
Sean
S
Donlevy
Department of Biology, University of Iowa, Iowa City, Iowa 52242 sarit-smolikove@uiowa.edu.
Sarit
S
Smolikove
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005854:Germ Cells / Q000201:enzymology / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008540:Meiosis / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009154:Mutation; D009865:Oocytes / Q000166:cytology; D011418:Prophase / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic
D029742:Caenorhabditis elegans Proteins; D011494:Protein Kinases; C577677:TAO kinase KIN-18, C elegans; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans
KIN-18; MPK-1; TAO; genetics of sex; meiosis; recombination