Usp14 is required for spermatogenesis and ubiquitin stress responses in Drosophila melanogaster

Deubiquitylating (DUB) enzymes free covalently linked ubiquitin moieties from ubiquitin-ubiquitin and ubiquitin-protein conjugates, and thereby maintain the equilibrium between free and conjugated ubiquitin moieties and regulate ubiquitin-mediated cellular processes. Here, we performed genetic analyses of mutant phenotypes in and demonstrate that loss of Usp14 function results in male sterility, with defects in spermatid individualization and reduced testicular free monoubiquitin levels. These phenotypes were rescued by germline-specific overexpression of wild-type Usp14. Synergistic genetic interactions with and cycloheximide sensitivity suggest that ubiquitin shortage is a primary cause of male sterility. In addition, is predominantly expressed in testes in , indicating a higher demand for this DUB in testes that is also reflected by testis-specific loss-of-function phenotypes. Collectively, these results suggest a major role of Usp14 in maintaining normal steady state free monoubiquitin levels during the later stages of spermatogenesis.This article has an associated First Person interview with the first author of the paper.