Role of Ubiquitin C-Terminal Hydrolase-L1 in Antipolyspermy Defense of Mammalian Oocytes1

Abstract

The ubiquitin-proteasome system regulates many cellular processes through rapid proteasomal degradation of ubiquitin-tagged proteins. Ubiquitin C-terminal hydrolase-L1 (UCHL1) is one of the most abundant proteins in mammalian oocytes. It has weak hydrolytic activity as a monomer and acts as a ubiquitin ligase in its dimeric or oligomeric form. Recently published data show that insufficiency in UCHL1 activity coincides with polyspermic fertilization; however, the mechanism by which UCHL1 contributes to this process remains unclear. Using UCHL1-specific inhibitors, we induced a high rate of polyspermy in bovine zygotes after in vitro fertilization. We also detected decreased levels in the monomeric ubiquitin and polyubiquitin pool. The presence of UCHL1 inhibitors in maturation medium enhanced formation of presumptive UCHL1 oligomers and subsequently increased abundance of K63-linked polyubiquitin chains in oocytes. We analyzed the dynamics of cortical granules (CGs) in UCHL1-inhibited oocytes; both migration of CGs toward the cortex during oocyte maturation and fertilization-induced extrusion of CGs were impaired. These alterations in CG dynamics coincided with high polyspermy incidence in in vitro-produced UCHL1-inhibited zygotes. These data indicate that antipolyspermy defense in bovine oocytes may rely on UCHL1-controlled functioning of CGs.

Role of the Ubiquitin C-Terminal Hydrolase L1-Modulated Ubiquitin Proteasome System in Auditory Cortex Senescence

“…3G, H). Our results coincide with a previous study showing that inhibition of UCHL1 reduced the levels of monoubiquitin and ubiquitinated proteins [42]. Monoubiquitin plays an important role in proteolysis [43].…”

Sperm proteasome and fertilization

“…In contrast, preinjection of oocytes with UA or with anti-UCHL3 antibodies (UCHL1 accumulates in oocyte cortex) inhibited sperm incorporation in the ooplasm (Mtango et al 2009). This could be due to a yet to be elucidated function of UCHs in the regulation of oocyte-cortical Sperm proteasome and fertilization cytoskeleton, or to a recently demonstrated effect of UCHL1-block on cortical granule migration and maturation (Susor et al 2010). Altogether, the above data explain why the inhibition of sperm DUBs during IVF has an effect opposite to that of IVF-blocking proteasomal inhibitors.…”

“…However, their C-terminal hydrolase enzymatic activity varies between individual family members and a preference for certain substrates has been suggested for individual UCH family members (Kurihara et al 2000). Of particular interest to us are UCHL1 present in the sperm acrosome and oocyte cortex, and UCHL3 present in the meiotic spindle of porcine, bovine, murine, and primate oocytes (Yi et al 2007b, Mtango et al 2009, Susor et al 2010. Proteomic analysis suggests that UCHL1 is one of the most abundant proteins in mammalian oocytes (Ellederova et al 2004, Massicotte et al 2006.…”

Sperm Proteasome as a Putative Egg Coat Lysin in Mammals

“…Block of sperm UCHL3 increases porcine polyspermy in vitro while supplementation of recombinant UCHs to IVF media reduced polyspermy and increased the rate of monospermic fertilization (Yi et al 2007b ). Interference with bovine oocyte UCHL1 alters cortical granule maturation and causes polyspermy (Susor et al 2010 ). Block of murine oocyte UCHL1 and UCHL3 prevents sperm incorporation in the ooplasm and causes meiotic spindle anomalies and polar body extrusion defects (Mtango et al 2012a , b ).…”