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

Dev Biol. 2007 Feb 15;302(2):438-47. doi: 10.1016/j.ydbio.2006.09.053. Epub 2006 Oct 5.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Adenosine Triphosphatases / metabolism*
  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology*
  • Meiosis / physiology*
  • Microtubules / metabolism
  • Mitosis
  • Mutation
  • Protein-Serine-Threonine Kinases / physiology*
  • Protein-Tyrosine Kinases / physiology*
  • Ubiquitin-Protein Ligase Complexes / genetics
  • Ubiquitin-Protein Ligase Complexes / physiology*
  • Ubiquitin-Protein Ligases / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Mel-26 protein, C elegans
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • Dyrk kinase
  • MBK-2 protein, C elegans
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Adenosine Triphosphatases
  • MEI-1 protein, C elegans