The AAA-ATPase FIGL-1 controls mitotic progression, and its levels are regulated by the CUL-3MEL-26 E3 ligase in the C. elegans germ line.
Members of the AAA-ATPase (ATPases associated with diverse cellular activities) family use the energy from ATP hydrolysis to disrupt protein complexes involved in many cellular processes. Here, we report that FIGL-1 (Fidgetin-like 1), the single Caenorhabditis elegans homolog of mammalian fidgetin and fidgetin-like 1 AAA-ATPases, controls progression through mitosis in the germ line and the early embryo. Loss of figl-1 function leads to the accumulation of mitotic nuclei in the proliferative zone of the germ line, resulting in sterility owing to depletion of germ cells. Like the AAA-ATPase MEI-1 (also known as katanin), FIGL-1 interacts with microtubules and with MEL-26, a specificity factor of CUL-3-based E3 ligases involved in targeting proteins for ubiquitin-dependent degradation by the 26S proteasome. In the germ line, FIGL-1 is enriched in nuclei of mitotic cells, but it disappears at the transition into meiosis. Conversely, MEL-26 expression is low in nuclei of the mitotic zone and induced during meiosis. FIGL-1 accumulates in the germ line and spreads to the meiotic zone after inactivation of mel-26 or cul-3 in vivo. We conclude that degradation of FIGL-1 by the CUL-3MEL-26 E3 ligase spatially restricts FIGL-1 function to mitotic cells, where it is required for correct progression through mitosis.
Luke-Glaser
Sarah
S
Institute of Biochemistry, HPM G8, ETH Hönggerberg, 8093 Zürich, Switzerland.
Pintard
Lionel
L
Tyers
Mike
M
Peter
Matthias
M
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D007246:Infertility / Q000235:genetics / Q000378:metabolism; D000074201:Katanin; D008540:Meiosis / Q000502:physiology; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D044842:Cullin Proteins; C510976:CUL-3 protein, C elegans; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D000251:Adenosine Triphosphatases; C496225:figl-1 protein, C elegans; D000074201:Katanin