Open AccessA genetic screen in Drosophila reveals an unexpected role for the KIP1 ubiquitination-promoting complex in male fertility
Author(s) -
Weizhe Li,
Jinqing Liang,
Patricia Outeda,
Stacey Turner,
Barbara T. Wakimoto,
Terry Watnick
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1009217
Subject(s) - drosophila melanogaster , biology , sperm , flagellum , microbiology and biotechnology , genetics , phenocopy , motile cilium , cilium , drosophila (subgenus) , melanogaster , ubiquitin ligase , sperm motility , ubiquitin , mutant , gene
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 .