title: Mutations of a redundant alpha-tubulin gene affect Caenorhabditis elegans early embryonic cleavage via MEI-1/katanin-dependent and -independent pathways.
abstract: The C. elegans zygote supports both meiosis and mitosis within a common cytoplasm. The meiotic spindle is small and is located anteriorly, whereas the first mitotic spindle fills the zygote. The C. elegans microtubule-severing complex, katanin, is encoded by the mei-1 and mei-2 genes and is solely required for oocyte meiotic spindle formation; ectopic mitotic katanin activity disrupts mitotic spindles. Here we characterize two mutations that rescue the lethality caused by ectopic MEI-1/MEI-2. Both mutations are gain-of-function alleles of tba-2 alpha-tubulin. These tba-2 alleles do not prevent MEI-1/MEI-2 microtubule localization but do interfere with its activity. TBA-1 and TBA-2 are redundant for viability, but when katanin activity is limiting, TBA-2 is preferred over TBA-1 by katanin. This is similar to what we previously reported for the beta-tubulins. Removing both preferred alpha- and beta-isoforms results in normal development, suggesting that the katanin isoform preferences are not absolute. We conclude that while the C. elegans embryo expresses redundant alpha- and beta-tubulin isoforms, they nevertheless have subtle functional specializations. Finally, we identified a dominant tba-2 allele that disrupts both meiotic and mitotic spindle formation independently of MEI-1/MEI-2 activity. Genetic studies suggest that this tba-2 mutation has a "poisonous" effect on microtubule function.
authors.affiliation: Genes and Development Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, Alberta, Canada.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Lu
authors.forename: Paul E
authors.initials: PE
authors.lastname: Mains
mesh_terms: D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002970:Cleavage Stage, Ovum / Q000378:metabolism*; D000074201:Katanin; D008540:Meiosis / Q000235:genetics; D008870:Microtubules / Q000235:genetics; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000235:genetics; D014404:Tubulin / Q000235:genetics* / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D020033:Protein Isoforms; D014404:Tubulin; D000251:Adenosine Triphosphatases; C086678:MEI-1 protein, C elegans; C409220:MEI-2 protein, C elegans; D000074201:Katanin