title: Regulation of the MEI-1/MEI-2 Microtubule-Severing Katanin Complex in Early Caenorhabditis elegans Development.
abstract: After fertilization, rapid changes of the Caenorhabditis elegans cytoskeleton occur in the transition from meiosis to mitosis, requiring precise regulation. The MEI-1/MEI-2 katanin microtubule-severing complex is essential for meiotic spindle formation but must be quickly inactivated to allow for proper formation of the mitotic spindle. MEI-1/MEI-2 inactivation is dependent on multiple redundant pathways. The primary pathway employs the MEL-26 substrate adaptor for the CUL-3/cullin-based E3 ubiquitin ligase, which targets MEI-1 for proteosomal degradation. Here, we used quantitative antibody staining to measure MEI-1 levels to determine how other genes implicated in MEI-1 regulation act relative to CUL-3/MEL-26 The anaphase-promoting complex/cyclosome, APC/C, the DYRK (Dual-specificity tyrosine-regulated kinase), MBK-2, and the CUL-2-based E3 ubiquitin ligase act together to degrade MEI-1, in parallel to MEL-26/CUL-3 CUL-2 is known to keep MEL-26 low during meiosis, so CUL-2 apparently changes its target from MEL-26 in meiosis to MEI-1 in mitosis. RFL-1, an activator of cullin E3 ubiquitin ligases, activates CUL-2 but not CUL-3 for MEI-1 elimination. HECD-1 (HECT/Homologous to the E6AP carboxyl terminus domain) E3 ligase acts as a MEI-1 activator in meiosis but functions as an inhibitor during mitosis, without affecting levels of MEI-1 or MEI-2 Our results highlight the multiple layers of MEI-1 regulation that are required during the switch from the meiotic to mitotic modes of cell division.
authors.affiliation: Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, T2N 4N1, Canada.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Beard
authors.affiliation: Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, T2N 4N1, Canada.
authors.forename: Ryan B
authors.initials: RB
authors.lastname: Smit
authors.affiliation: Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, T2N 4N1, Canada.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Chan
authors.affiliation: Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, T2N 4N1, Canada mains@ucalgary.ca.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Mains
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D000074201:Katanin; D008540:Meiosis / Q000235:genetics; D008870:Microtubules; D008938:Mitosis / Q000235:genetics; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D046912:Multiprotein Complexes; D000251:Adenosine Triphosphatases; C086678:MEI-1 protein, C elegans; C409220:MEI-2 protein, C elegans; D000074201:Katanin
keywords: embryo; katanin; meiosis; microtubule severing; spindle