Specific aspects of the ubiquitin system in spermatogenesis

Abstract

The ubiquitin system is involved in numerous cellular processes, regulating the amounts and/or activities of specific proteins through posttranslational coupling with ubiquitin or ubiquitin-like proteins. In spermatogenesis, there appears to be a special requirement for certain components of the ubiquitin system, as exemplified in human and mouse by mutation of USP9Y and HR6B, respectively. Both genes encode proteins which take part in the ubiquitin system and are ubiquitously expressed, but their mutation generates no apparent phenotype other than male infertility. Different phases of mammalian spermatogenesis probably require different specialized activities of the ubiquitin system. It is anticipated that ubiquitination activities similar to those required during mitotic cell cycle regulation will play some role in control of the meiotic divisions. In spermatocytes, there is an intricate link among DNA repair, the ubiquitin system, and regulation of meiotic chromatin structure, as indicated by the co-localization of proteins involved in these processes on meiotic recombination complexes. HR6B and its nearly identical homolog HR6A are multiple function proteins, with ubiquitin-conjugating activity and essential roles in post-replication DNA repair. HR6B, possibly together with the ubiquitin-ligating enzyme mRAD1 8Sc, is most likely involved in chromatin re-organization during the meiotic and post-meiotic phases of spermatogenesis. Biochemical data indicate that, in particular during spermiogenesis, the general activity of the ubiquitin system is high, which most likely is related to the high requirement for massive breakdown of cytoplasmatic and nuclear proteins during this last phase of spermatogenesis.

The Region-Specific Functions of Two Ubiquitin C-Terminal Hydrolase Isozymes along the Epididymis

“…3 and 4A). Ubiquitin induction is important for regulating programmed cell death, which is a fundamental component of spermatogenesis [1,23,32]. Under specific circumstances, the caput epididymis contains a high level of ubiquitin, which may serve to maintain apoptotic mechanisms that eliminate abnormal spermatozoa [37].…”

Possible role of USP26 in patients with severely impaired spermatogenesis

“…In reviews, the presence and importance of ubiquitin and the ubiquitin pathway during gametogenesis was described, especially in the replacement of histones by protamines. 5,6,7 Another ubiquitin-specific protease gene involved in spermatogenesis is USP9Y. Brown et al 8 showed that Dffry, the mouse homologue of USP9Y, is expressed in the gametes.…”

Regulated expression of the ubiquitin protein ligase, E3Histone/LASU1/Mule/ARF‐BP1/HUWE1, during spermatogenesis

“…Indeed, cell proliferation occurs early in this process in spermatogonia, and ubiquitin-mediated protein degradation plays a key role in control of cell growth (reviewed in Reed, 2003). Although less well characterized, ubiquitination is also involved in meiosis (Baarends et al, 1999b(Baarends et al, , 2000 and so is likely implicated in spermatocyte development. Finally, during the cellular remodeling stage of spermiogenesis, many proteins are degraded in a temporally controlled manner, and so ubiquitination is also likely to be involved.…”