A genetic screen in Drosophila reveals an unexpected role for the KIP1 ubiquitination-promoting complex in male fertility.
A genetic screen in Drosophila reveals an unexpected role for the KIP1 ubiquitination-promoting complex in male fertility.
复制标题
DOI：
10.1371/journal.pgen.1009217
复制
发表时间：
2020-12
期刊：
影响因子：
4.5
通讯作者：
Watnick T
中科院分区：
文献类型：
--
作者：
Li W;Liang J;Outeda P;Turner S;Wakimoto BT;Watnick T
多囊蛋白-2 通道的一个统一特征是它们定位于初级和运动纤毛/鞭毛。在果蝇中，果蝇多囊蛋白-2 同源物 Amo 是精子发育早期的一种 ER 蛋白，但该蛋白最终必须聚集在成熟精子的鞭毛尖端才能发挥全部功能。缺乏适当的 Amo 定位的雄性果蝇由于精子活力异常和精子储存失败而无法生育。我们进行了正向遗传筛选，以确定介导 Amo 纤毛运输的其他蛋白质。在这里，我们报道了果蝇 KPC1 和 KPC2 的同源物，它们组成了哺乳动物 KIP1 泛素化促进复合物 (KPC)，形成了 Amo 精子尾尖定位所需的保守单元。雄性果蝇缺乏 KPC1 或 KPC2 表型 amo 突变体，并且由于精子储存失败而处于不育状态。 KPC 是由 KPC1（一种 E3 连接酶）和 KPC2（或 UBAC1）（一种衔接蛋白）组成的异二聚体。与哺乳动物果蝇一样，KPC1 和 KPC2 会发生物理相互作用，并在蛋白质水平上相互稳定。在果蝇中，KPC2 被单泛素化和磷酸化，这种修饰形式的蛋白质位于成熟精子中。 KPC1 和 KPC2 都不直接与 Amo 相互作用，但在精子鞭毛尖端的 Amo 附近检测到它们。总之，我们发现了一种与果蝇雄性生育力有关的新复合物。在果蝇中，多囊蛋白-2 同源物 Amo 存在于精子尾尖的限制区域，在那里它介导定向精子迁移和适当的精子储存。参与 Amo 转运至这一独特亚细胞结构域的因素尚不清楚。我们筛选了一组雄性不育果蝇 EMS 突变体的 Amo 错误定位，以获得有关可能参与该过程的蛋白质的线索。在这里，我们报道了果蝇 KPC1 和 KPC2 的同源物，它们构成了哺乳动物 KIP1 泛素化促进复合物 (KPC) 的核心，是 Amo 到达精子尾尖所必需的。总之，我们发现了 KIP1 泛素化促进复合物在果蝇精子和男性生育能力中的新作用。
A unifying feature of polycystin-2 channels is their localization to both primary and motile cilia/flagella. In Drosophila melanogaster, the fly polycystin-2 homologue, Amo, is an ER protein early in sperm development but the protein must ultimately cluster at the flagellar tip in mature sperm to be fully functional. Male flies lacking appropriate Amo localization are sterile due to abnormal sperm motility and failure of sperm storage. We performed a forward genetic screen to identify additional proteins that mediate ciliary trafficking of Amo. Here we report that Drosophila homologues of KPC1 and KPC2, which comprise the mammalian KIP1 ubiquitination-promoting complex (KPC), form a conserved unit that is required for the sperm tail tip localization of Amo. Male flies lacking either KPC1 or KPC2 phenocopy amo mutants and are sterile due to a failure of sperm storage. KPC is a heterodimer composed of KPC1, an E3 ligase, and KPC2 (or UBAC1), an adaptor protein. Like their mammalian counterparts Drosophila KPC1 and KPC2 physically interact and they stabilize one another at the protein level. In flies, KPC2 is monoubiquitinated and phosphorylated and this modified form of the protein is located in mature sperm. Neither KPC1 nor KPC2 directly interact with Amo but they are detected in proximity to Amo at the tip of the sperm flagellum. In summary we have identified a new complex that is involved in male fertility in Drosophila melanogaster. In Drosophila, the polycystin-2 homologue, Amo, is found in a restricted area at the tip of the sperm tail where it mediates directed sperm migration and proper sperm storage. The factors involved in Amo trafficking to this distinctive subcellular domain are unknown. We screened a collection of male sterile Drosophila EMS mutants for mislocalization of Amo to gain clues about what proteins that might be involved in this process. Here we report that fly homologues of KPC1 and KPC2 which, form the core of the mammalian KIP1 ubiquitination-promoting complex (KPC) are required for Amo to reach the tip of the sperm tail. In summary, we have uncovered a novel role for the KIP1 ubiquitination-promoting complex in Drosophila sperm and male fertility.
登录
查看更多内容
影响因子：
64.8
作者：
Barr, MM;Sternberg, PW
通讯作者：
Sternberg, PW
影响因子：
4
作者：
Geng, L;Okuhara, D;Somlo, S
通讯作者：
Somlo, S
影响因子：
2.1
作者：
Kravtsova-Ivantsiv, Yelena;Ciechanover, Aaron
通讯作者：
Ciechanover, Aaron
DOI：
10.1016/j.biocel.2015.08.005
发表时间：
2015-11-01
影响因子：
4
作者：
Hnit, Su Su Thae;Xie, Chanlu;Dong, Qihan
通讯作者：
Dong, Qihan
DOI：
10.1073/pnas.0535280100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Gong, WJ;Golic, KG
通讯作者：
Golic, KG