Proteomics of post-translational modifications of mammalian spermatozoa

Abstract

It is hard to fathom that one of the most highly differentiated cells in the body, the spermatozoon, spends over half of its developmental life without the capacity for nuclear protein biosynthesis. This is even more incredible when considering that protein synthesis is switched off long before the sperm is mature. As such, in order to obtain full functionality, spermatozoa rely on post-translational modifications (PTM) of existing proteins. Many PTM have been shown to play a role in the development of a sperm cell. These include phosphorylation and glycosylation events that occur both in the epididymis and during capacitation. In addition, several other PTM such as disulfide cross-linking, ubiquitination, acetylation and methylation all play a role to both develop and enable a spermatozoon to achieve its final destiny.

Factors and pathways involved in capacitation: how are they regulated?

“…This converts ATP to cAMP [16]. The cyclic nucleotide then dissociates the sperm-specific PKA regulatory subunits from the catalytic subunits [114]. Further study reveals that the phosphorylation of tyrosine is altered in sAC Null Sperm.…”

Immune regulatory molecules as modifiers of semen and fertility: A review

“…These can be supplemented with gene ontology databases and analysis resources for annotation, visualization, and integrated discovery (DAVID; Huang, Sherman, & Lempicki, ) and protein analysis through evolutionary relationships (PANTHER; Thomas et al, ) classification systems, search tools for the retrieval of interacting genes/proteins (STRING): functional protein association networks (Jensen et al, ). In concert, they have helped to define biological significance, molecular functionality, cellular compartment, and pathways advancing our understanding of the cascade of events associated with immune regulatory molecules and their modifications that alter the fertility status of the individual (Baker, ). For example, ASA antigens listed in Table subjected to STRING protein‐interaction analysis revealed 88 different significant functional reproductive biological processes (Supplementary Data 1).…”

Flow cytometry in Spermatology: A bright future ahead

“…Traditional whole‐sperm proteomic approaches such as 2D polyacrylamide gel electrophoresis, mass spectrometry (MS) and differential in‐gel electrophoresis have allowed for the identification of numerous sperm‐specific proteins (Agarwal et al., ; du Plessis, Kashou, Benjamin, Yadav, & Agarwal, ). Studies of the sperm proteome have demonstrated how post‐translational modifications such as phosphorylation, glycosylation, proteolytic cleavage and mutation bring about physiological changes in spermatozoa function (Aitken & Baker, ; Baker, ). Furthermore, proteomic analysis has allowed for the study of spermatozoa in different functional states, for example immature vs. mature, uncapacitated vs. capacitated, normal vs. defective, all of which impact the reproductive potential of the male (Agarwal, Durairajanayagam, Halabi, Peng, & Vazquez‐Levin, ; Barazani, Agarwal, & Sabanegh, ; Gupta, Ghulmiyyah, Sharma, Halabi, & Agarwal, ; du Plessis et al., ).…”

“…Due to the silencing of nuclear transcription in ejaculated spermatozoa, post‐translational modifications of existing proteins are necessary for proper sperm function. These modifications include phosphorylation, glycosylation, disulphide cross‐linking, ubiquitination, acetylation and methylation (Baker, ).…”