Levels of the ubiquitin ligase substrate adaptor MEL-26 are inversely correlated with MEI-1/katanin microtubule-severing activity during both meiosis and mitosis.
The MEI-1/MEI-2 microtubule-severing complex, katanin, is required for oocyte meiotic spindle formation and function in C. elegans, but the microtubule-severing activity must be quickly downregulated so that it does not interfere with formation of the first mitotic spindle. Post-meiotic MEI-1 inactivation is accomplished by two parallel protein degradation pathways, one of which requires MEL-26, the substrate-specific adaptor that recruits MEI-1 to a CUL-3 based ubiquitin ligase. Here we address the question of how MEL-26 mediated MEI-1 degradation is triggered only after the completion of MEI-1's meiotic function. We find that MEL-26 is present only at low levels until the completion of meiosis, after which protein levels increase substantially, likely increasing the post-meiotic degradation of MEI-1. During meiosis, MEL-26 levels are kept low by the action of another type of ubiquitin ligase, which contains CUL-2. However, we find that the low levels of meiotic MEL-26 have a subtle function, acting to moderate MEI-1 activity during meiosis. We also show that MEI-1 is the only essential target for MEL-26, and possibly for the E3 ubiquitin ligase CUL-3, but the upstream ubiquitin ligase activating enzyme RFL-1 has additional essential targets.
Genes and Development Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada T2N 4N1.
Jacque-Lynne F A
JL
Johnson
Chenggang
C
Lu
Eko
E
Raharjo
Karen
K
McNally
Francis J
FJ
McNally
Paul E
PE
Mains
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D044842:Cullin Proteins / Q000378:metabolism*; D000074201:Katanin; D008540:Meiosis; D008870:Microtubules; D008938:Mitosis
D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D044842:Cullin Proteins; C114960:Mel-26 protein, C elegans; C491027:cul-2 proteins, C elegans; D000251:Adenosine Triphosphatases; C086678:MEI-1 protein, C elegans; D000074201:Katanin