The C. elegans anaphase promoting complex and MBK-2/DYRK kinase act redundantly with CUL-3/MEL-26 ubiquitin ligase to degrade MEI-1 microtubule-severing activity after meiosis.
The C. elegans embryo supports both meiotic and mitotic spindles, requiring careful regulation of components specific to each spindle type. The MEI-1/katanin microtubule-severing complex is required for meiosis but must be inactivated prior to mitosis. Downregulation of MEI-1 depends on MEL-26, which binds MEI-1, targeting it for degradation by the CUL-3 E3 ubiquitin ligase complex. Here we report that other protein degradation pathways, involving the anaphase promoting complex (APC) and the MBK-2/DYRK kinase, act in parallel to MEL-26 to inactivate MEI-1. At 25 degrees all mel-26(null) embryos die due to persistence of MEI-1 into mitosis, but at 15 degrees a significant portion of embryos hatch due to lower levels of ectopic MEI-1, suggesting that a redundant pathway also regulates MEI-1 degradation at 15 degrees. Previously the MBK-2/DYRK kinase was suggested to trigger MEL-26 mediated MEI-1 degradation. However, mbk-2 enhances the incomplete lethality of mel-26(null) at 15 degrees, arguing that MEL-26 acts in parallel to MBK-2. APC mutants behave similarly. In mel-26 embryos, ectopic MEI-1 remains until the onset of gastrulation, but in mbk-2; apc embryos, MEI-1 only persists through the first mitosis. We propose that mbk-2 and apc couple the initial phase of MEI-1 degradation to meiotic exit, after which MEL-26 completes MEI-1 degradation.
Lu
Chenggang
C
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Mains
Paul E
PE
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism* / Q000502:physiology*; D008540:Meiosis / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D000097603:Dyrk Kinases
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D064173:Anaphase-Promoting Complex-Cyclosome; D029742:Caenorhabditis elegans Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D000097603:Dyrk Kinases; C114960:Mel-26 protein, C elegans; C478059:MBK-2 protein, C elegans; C086678:MEI-1 protein, C elegans