Abstract
The human orthologue of the tumor suppressor protein FBW7 is encoded by the Drosophila archipelago (ago) gene. Ago is an F-box protein that gives substrate specificity to its SCF ubiquitin ligase complex. It has a central role in multiple biological processes in a tissue-specific manner such as cell proliferation, cellular differentiation, hypoxia-induced gene expression. Here we present a previously unknown tissue-specific role of Ago in spermatid differentiation. We identified a classical mutant of ago which is semi-lethal and male-sterile. During the characterization of ago function in testis, we found that ago plays role in spermatid development, following meiosis. We confirmed spermatogenesis defects by silencing ago by RNAi in testes. The ago mutants show multiple abnormalities in elongating and elongated spermatids, including aberration of the cyst morphology, malformed mitochondrial structures, and individualization defects. Additionally, we determined the subcellular localization of Ago protein with mCherry-Ago transgene in spermatids. Our findings highlight the potential roles of Ago in different cellular processes of spermatogenesis, like spermatid individualization, and regulation of mitochondrial morphology.
Highlights
Drosophila melanogaster testis is a suitable model to follow the process of s permatogenesis[1,2]
There are multiple ubiquitin ligases known to have a role in the different steps of spermatogenesis (e.g.: Parkin, Ntc/Cul1/SkpA-SCFNtc)[7,8], and testis-specific proteasome subunits are emphasizing the ubiquitin–proteasome system’s (UPS) r ole[9]
Directed protein degradation is a crucial requirement of the spermatid individualization in Drosophila
Summary
Drosophila melanogaster testis is a suitable model to follow the process of s permatogenesis[1,2]. During Drosophila spermatogenesis from a single spermatogonia sixty-four sperms are being produced, through mitotic and meiotic cell divisions and intensive cellular remodeling. Spermatocytes undergo a maturing process, they have high transcriptional activity until meiosis and the accumulated transcripts contribute to the development of the transcriptionally mostly inactive post-meiotic stages[3]. Individualization, the process which establishes the individual sperms starts with the formation of the individualization complex (IC), which contains the F-actin-rich cone-shaped investment cones that are forming around the elongated nuclei. E3 ligases can mark proteins for time and tissue-specific degradation they have a role in many different cellular processes such as cell cycle, epigenetic regulation, mitophagy, etc.[12]. We show that lack of Ago resulted in male sterility and abnormal individualization of spermatids, including abnormal nuclear and mitochondrial structure
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