Caenorhabditis elegans p97 controls germline-specific sex determination by controlling the TRA-1 level in a CUL-2-dependent manner
Caenorhabditis elegans p97 controls germline-specific sex determination by controlling the TRA-1 level in a CUL-2-dependent manner
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DOI：
10.1242/jcs.052415
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发表时间：
2009-10
影响因子：
4
通讯作者：
Yohei Sasagawa;M. Otani;N. Higashitani;A. Higashitani;Ken Sato;T. Ogura;K. Yamanaka
中科院分区：
文献类型：
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作者：
Yohei Sasagawa;M. Otani;N. Higashitani;A. Higashitani;Ken Sato;T. Ogura;K. Yamanaka
P97(秀丽线虫中的CDC-48)是一种泛素选择性的AAA(与多种细胞活动相关的ATPase)伴侣，其关键功能是分解蛋白质复合体。P97在多种细胞过程中发挥作用，包括内质网(ER)相关的降解、膜融合、减数分裂和有丝分裂进程。然而，它在发育过程中的细胞功能尚未被阐明。在这里，我们提供的数据表明，p97参与了线虫两性生殖系从精子发生到卵子发生的转换。我们发现CDC-48.1缺失突变体比野生型产生的精子更少，因此表现出更小的孵化大小。CDC-48.1突变抑制了fbf-1和fem-3(Gf)突变体的精子过度生产表型。此外，p97/CDC-48-UFD-1-NPL-4复合体与E3泛素连接酶CUL-2复合体通过NPL-4与Elongin C结合，并且在CDC-48.1突变体中积累了TRA-1A，它是性别决定通路的末端效应因子，受CuL-2介导的蛋白分解调节。此外，还需要蛋白酶体活性来确定孵化仔数和精-卵母细胞的转换。我们的结果表明，线虫p97/CDC-48-UFD-1-NPL-4复合体通过调节CuL-2介导的TRA-1A蛋白酶体降解来控制精子-卵母细胞开关。
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.