Interactors and targeted substrates of UBL7 in mouse testis and sperm

ABSTRACT: Spermiogenesis is a tightly regulated process to produce mature sperm cells. The ubiquitin-proteasome system (UPS) plays a crucial role in controlling protein half-life and is essential for spermiogenesis. In this study, we demonstrate that UBL7, a testis-enriched UBL-UBA protein, is indispensable for sperm formation. UBL7 interacts with the valosin-containing protein (VCP) complex and proteasomes, and shuttles substrates between them. Notably, UBL7 slows down the degradation rates of substrates involved in endoplasmic reticulum-associated degradation (ERAD) within cells. Through tandem mass tag (TMT)-labeled quantitative proteomics of sperm from Ubl7+/- and Ubl7-/- epididymis, we found lots of proteins were decreased in Ubl7-/- sperm, including critical factors involved in ATP metabolism and glycolytic process. Through a two-step immunoprecipitation method, we identify several essential factors in spermatids that are protected by UBL7, including factors involved in the development of manchette (such as IFT140), head-tail coupling apparatus (such as SPATA20) and cytoplasmic droplets (such as HK1 and SLC2a3). In summary, our findings highlight UBL7 as a guardian that protects crucial factors from excessive degradation and thereby ensures successful spermiogenesis.

ORGANISM(S): Mus Musculus

SUBMITTER: Fengchao Wang  

PROVIDER: PXD061424 | iProX | Tue Mar 04 00:00:00 GMT 2025

REPOSITORIES: iProX