Ubiquitin-Proteasome System in Mammalian Sperm Function
Summary
The ubiquitin-proteasome system (UPS) orchestrates targeted protein degradation and remodelling in mammalian sperm, underpinning functional maturation, fertilisation and post-fertilisation events. In the male germline, transcription and translation are halted during later stages of spermiogenesis, rendering proteostasis through post-translational modification essential. Ubiquitin molecules, covalently attached to protein substrates, tag unwanted or damaged proteins for recognition by the 26S proteasome, a large multicatalytic protease complex. The UPS regulates sperm capacitation by removing or processing specific surface and acrosomal proteins, thereby mediating membrane reorganisation, signalling cascades such as protein kinase A (PKA) activation, and the acrosome reaction. Beyond capacitation, proteasomes modulate the dynamics of sperm-egg interactions, including zona pellucida penetration via degradation of zona proteins, and contribute to paternal mitochondrial elimination after fertilisation in concert with autophagy pathways. Dysregulation of UPS activity is associated with infertility phenotypes, highlighting its importance for reproductive success and potential as a target for contraception. Recent advances have revealed compartment-specific proteasome regulators and substrates within sperm cells, as well as crosstalk between proteasomal proteolysis and signal transduction networks, underscoring the multifaceted role of the UPS in sperm biology and early embryonic development.
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Technical terms
Ubiquitin: A small protein that is covalently attached to targets to mark them for degradation or other regulatory fates.
Proteasome: A multicatalytic protein complex that recognises ubiquitinated substrates and degrades them into peptides.
Capacitation: A physiological maturation process that sperm undergo in the female reproductive tract to gain fertilising ability.
Acrosome reaction: A regulated exocytosis of the acrosomal vesicle at the sperm head, enabling penetration of the egg coat.
Mitophagy: Selective autophagic clearance of mitochondria, here applied to paternal mitochondrial elimination after fertilisation.
References
- The Ubiquitin-Proteasome System Participates in Sperm Surface Subproteome Remodeling during Boar Sperm Capacitation. Biomolecules (2023).
- Sperm Proteasomes Degrade Sperm Receptor on the Egg Zona Pellucida during Mammalian Fertilization. PLOS ONE (2011).
- Compartmentalization of the proteasome-interacting proteins during sperm capacitation. Scientific Reports (2019).
- Proteostasis in the Male and Female Germline: A New Outlook on the Maintenance of Reproductive Health. Frontiers in Cell and Developmental Biology (2021).
- Protein Kinase A (PRKA) Activity Is Regulated by the Proteasome at the Onset of Human Sperm Capacitation. Cells (2021).
- Mammalian Cell-Free System Recapitulates the Early Events of Post-Fertilization Sperm Mitophagy. Cells (2021).
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