Dominant mutations in the Caenorhabditis elegans Myt1 ortholog wee-1.3 reveal a novel domain that controls M-phase entry during spermatogenesis.
Regulatory phosphorylation of the Cdc2p kinase by Wee1p-type kinases prevents eukaryotic cells from entering mitosis or meiosis at an inappropriate time. The canonical Wee1p kinase is a soluble protein that functions in the eukaryotic nucleus. All metazoa also have a membrane-associated Wee1p-like kinase named Myt1, and we describe the first genetic characterization of this less well-studied kinase. The Caenorhabditis elegans Myt1 ortholog is encoded by the wee-1.3 gene, and six dominant missense mutants prevent primary spermatocytes from entering M phase but do not affect either oocyte meiosis or any mitotic division. These six dominant wee-1.3(gf) mutations are located in a four amino acid region near the C terminus and they cause self-sterility of hermaphrodites. Second-site intragenic suppressor mutations in wee-1.3(gf) restore self-fertility to these dominant sterile hermaphrodites, permitting genetic dissection of this kinase. Ten intragenic wee-1.3 suppressor mutations were recovered and they form an allelic series that includes semi-dominant, hypomorphic and null mutations. These mutants reveal that WEE-1.3 protein is required for embryonic development, germline proliferation and initiation of meiosis during spermatogenesis. This suggests that a novel, sperm-specific pathway negatively regulates WEE-1.3 to allow the G2/M transition of male meiosis I, and that dominant wee-1.3 mutants prevent this negative regulation.
Lamitina
S Todd
ST
Department of Biology, Emory University, Atlanta, GA 30322, USA.
L'Hernault
Steven W
SW
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins; D018509:DNA, Helminth / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D017238:Genes, Helminth; D008297:Male; D008540:Meiosis / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013091:Spermatogenesis / Q000235:genetics*; D013489:Suppression, Genetic
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D018509:DNA, Helminth; D009687:Nuclear Proteins; C490678:wee-1.3 protein, C elegans; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases