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First published online 22 September 2009
doi: 10.1242/jcs.052415


Journal of Cell Science 122, 3663-3672 (2009)
Published by The Company of Biologists 2009
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Research Article

Caenorhabditis elegans p97 controls germline-specific sex determination by controlling the TRA-1 level in a CUL-2-dependent manner

Yohei Sasagawa1,*,{ddagger}, Mieko Otani2, Nahoko Higashitani3, Atsushi Higashitani3, Ken Sato4, Teru Ogura1 and Kunitoshi Yamanaka1,*,§

1 Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
2 Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan
3 The Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba, Sendai 980-8577, Japan
4 Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-cho, Maebashi 371-8512, Japan

§ Author for correspondence (yamanaka{at}gpo.kumamoto-u.ac.jp)

Accepted 29 July 2009

p97 (CDC-48 in Caenorhabditis elegans) is a ubiquitin-selective AAA (ATPases associated with diverse cellular activities) chaperone and its key function is to disassemble protein complexes. p97 functions in diverse cellular processes including endoplasmic reticulum (ER)-associated degradation, membrane fusion, and meiotic and mitotic progression. However, its cellular functions in development have not yet been clarified. Here, we present data that p97 is involved in the switch from spermatogenesis to oogenesis in the germline of the C. elegans hermaphrodite. We found that the cdc-48.1 deletion mutant produced less sperm than the wild type and thus showed a decreased brood size. The cdc-48.1 mutation suppressed the sperm-overproducing phenotypes of fbf-1 and fem-3(gf) mutants. In addition, the p97/CDC-48–UFD-1–NPL-4 complex interacted with the E3 ubiquitin ligase CUL-2 complex via NPL-4 binding to Elongin C. Furthermore, TRA-1A, which is the terminal effector of the sex determination pathway and is regulated by CUL-2-mediated proteolysis, accumulated in the cdc-48.1 mutant. Proteasome activity was also required for the brood size determination and sperm-oocyte switch. Our results demonstrate that the C. elegans p97/CDC-48–UFD-1–NPL-4 complex controls the sperm-oocyte switch by regulating CUL-2-mediated TRA-1A proteasome degradation.

Key words: AAA family, C. elegans, p97/Cdc48p, Sex determination, TRA-1, Ubiquitin ligase


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