DepartmentMolecular Cell Biology
Publication date1-Aug-2012

Yohei Sasagawa, Atsushi Higashitani, Takeshi Urano, Teru Ogura, and Kunitoshi Yamanaka (2012) CDC-48/p97 is required for proper meiotic chromosome segregation via controlling AIR-2/Aurora B kinase localization in Caenorhabditis elegans . J. Struct. Biol. 179: 104-111.

CDC-48/p97 is a AAA (ATPases associated with diverse cellular activities) chaperone involved in protein conformational changes such as the disassembly of protein complexes. We previously reported thatCaenorhabditis elegans CDC-48.1 and CDC-48.2 (CDC-48s) are essential for the progression of meiosis I metaphase. Here, we report that CDC-48s are required for proper chromosome segregation during meiosis in C. elegans. In wild-type worms, at the diakinesis phase, phosphorylation of histone H3, one of the known substrates of aurora B kinase (AIR-2), on meiosis I chromatids correlated with AIR-2 localization at the cohesion sites of homologous chromatids. Conversely, depletion of CDC-48s resulted in a significant expansion of signals for AIR-2 and phosphorylated histone H3 over the entire length of meiotic chromosomes, leading to defective chromosome segregation (Figure), while the total amount of AIR-2 in lysates was not changed by the depletion of CDC-48s. The defective segregation of meiotic chromosomes caused by the depletion of CDC-48s was suppressed by the simultaneous depletion of AIR-2 and is similar to that observed following the depletion of protein phosphatase 1 (PP1) phosphatases. However, the amount and localization of PP1 were not changed by the depletion of CDC-48s. These results suggest that CDC-48s control the restricted localization of AIR-2 to the cohesion sites of homologous chromatids in meiosis I.



Figure. (A) Schematic time-lapse images of meiotic I and II are shown. Four-dimensional fluorescence images of different meiotic stages in RNAi control (B) and CDC-48-depleted (C) embryos of histone H2B::GFP strains. Bars, 10 m m. (D) Localization of chromosomal AIR-2 on bivalent chromosomes in matured oocytes. Bars, 2 m m.