Human sperm phosphoproteome reveals differential phosphoprotein signatures that regulate human sperm motility

Martín‐Hidalgo, David; Serrano, Rebeca; Zaragoza, Concepción; García‐Marín, Luis J.; Bragado, Marı́a Julia

doi:10.1016/j.jprot.2020.103654

Cited by 26 publications

(44 citation statements)

References 29 publications

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“…Until recently, the phosphoproteome and ubiquitylome were most frequently reported in mammalian cells and tissues in human and murine (Danielsen et al, 2011; Huttlin et al, 2010; Kim et al, 2011; Martin‐Hidalgo et al, 2020; Qi et al, 2014; Wagner et al, 2012; Zahedi et al, 2008). A comparative phosphoproteome was performed to find the phosphorylation difference between buffalo epididymal sperm (Table S1) and mouse (Huttlin et al, 2010; https://phosphomouse.hms.harvard.edu/index.php).…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of phosphoproteome and ubiquitylome in epididymal sperm of buffalo (Bubalus bubalis)

Peng-fei

Huang

et al. 2020

Molecular Reproduction Devel

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In mammals, sperm need to mature in the epididymis to gain fertilization competency. However, the molecular mechanism underlying buffalo sperm maturation remains elusive. Exploring sperm physiology at the posttranslational modification (PTM) level could help to develop our understanding of these mechanisms. Protein phosphorylation and ubiquitination are major PTMs in the regulation of many biological processes. In the present study, to our knowledge, we report the first phosphoproteome and ubiquitylome of sperm collected from the caput, corpus, and cauda segments of the epididymis using liquid chromatography–mass spectrometry combined with affinity purification. In total, 647 phosphorylation sites in 294 proteins and 1063 ubiquitination sites in 446 proteins were characterized. Some of these proteins were associated with cellular developmental processes and energy metabolic pathways. Interestingly, 84 proteins were both phosphorylated and ubiquitinated, simultaneously. Some of these proteins were involved in, for example, spermatogenesis, reproduction, and spermatid development. Taken together, these data provide a theoretical basis for further functional analysis of phosphorylation and ubiquitination in epididymal sperm of buffalo and other mammals, and serve as an important resource for exploring the physiological mechanism underlying sperm maturation.

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Section: Discussionmentioning

confidence: 99%

Integrated analysis of phosphoproteome and ubiquitylome in epididymal sperm of buffalo (Bubalus bubalis)

Peng-fei

Huang

et al. 2020

Molecular Reproduction Devel

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“…According to our IPA results regarding the GP6 signaling pathway, GSK-3 was activated in the Cap 90/0 and Cap 90/60 comparison, while in the Cap 60/0 comparison, GSK-3 was inhibited; thus, GSK-3 was inhibited or phosphorylated in the Cap 60 dataset. A previous phosphoproteome study showed abundant GSK-3α phosphorylation in high-motility human sperm [ 37 ]. Li’s study demonstrated that H2AX phosphorylation can be abolished by PI3K inhibition and therefore rescue DNA in spermatozoa from oxidative damage [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation

Syifa

Yang

et al. 2020

IJMS

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Protein phosphorylation can induce signal transduction to change sperm motility patterns during sperm capacitation. However, changes in the phosphorylation of sperm proteins in mice are still incompletely understood. Here, capacitation-related phosphorylation in mouse sperms were firstly investigated by label-free quantitative (LFQ) phosphoproteomics coupled with bioinformatics analysis using ingenuity pathway analysis (IPA) methods such as canonical pathway, upstream regulator, and network analysis. Among 1632 phosphopeptides identified at serine, threonine, and tyrosine residues, 1050 novel phosphosites, corresponding to 402 proteins, were reported. Gene heatmaps for IPA canonical pathways showed a novel role for GSK-3 in GP6 signaling pathways associated with capacitation for 60 min. At the same time, the reduction of the abundant isoform-specific GSK-3α expression was shown by western blot (WB) while the LFQ pY of this isoform slightly decreased and then increased. The combined results from WB and LFQ methods explain the less inhibitory phosphorylation of GSK-3α during capacitation and also support the predicted increases in its activity. In addition, pAKAP4 increased at the Y156 site but decreased at the Y811 site in a capacitated state, even though IPA network analysis and WB analysis for overall pAKAP revealed upregulated trends. The potential roles of GSK-3 and AKAP4 in fertility are discussed.

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“…Phosphorylation, as the most important PTM, allows rapid control of the activity of signaling and regulatory proteins, which is essential in the regulation of sperm function (Parte et al, 2012;Porambo et al, 2012;Dacheux and Dacheux, 2014). In recent years, the phosphoproteomics strategy has been widely used to uncover the molecular mechanisms of capacitation, sperm maturation, sperm motility, and infertility in human, mice, or other animals (Ficarro et al, 2003;Wang et al, 2015;Gazo et al, 2017;Castillo et al, 2019;Nixon et al, 2019b;Urizar-Arenaza et al, 2019;Martin-Hidalgo et al, 2020). However, a much deeper analysis of the phospho-regulation in the porcine sperm has not been conducted yet.…”

Section: Sperm Phosphoproteome Differences Between Yorkshire and Duroc Boarmentioning

confidence: 99%

“…Due to the extensive application of "omics" technology for system biology, tremendous progress has been made in recent years on protein function research through global proteome analysis and its complex interaction in response to specific disturbance (Larance and Lamond, 2015;Dai et al, 2019a). Proteomics has also been widely used in the study of human and other animal sperm, which can reflect the protein composition, distribution, and function of sperm cells from a macro perspective, and indicated that sperm proteins play essential functional roles and contribute to vital biological processes such as spermatogenesis, sperm motility, sperm capacitation, fertilization, and male infertility (Chalmel and Rolland, 2015;Baker, 2016;Maciel et al, 2019;Agarwal et al, 2020;Martin-Hidalgo et al, 2020). Therefore, quantitative proteomics analysis is a potent tool for understanding the quality variation in sperm functions.…”

Section: Introductionmentioning

confidence: 99%

Comparative Proteomics and Phosphoproteomics Analysis Reveal the Possible Breed Difference in Yorkshire and Duroc Boar Spermatozoa

Han

Ma³

et al. 2021

Front. Cell Dev. Biol.

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Sperm cells are of unique elongated structure and function, the development of which is tightly regulated by the existing proteins and the posttranslational modifications (PTM) of these proteins. Based on the phylogenetic relationships of various swine breeds, Yorkshire boar is believed to be distinctly different from Duroc boar. The comprehensive differential proteomics and phosphoproteomics profilings were performed on spermatozoa from both Yorkshire and Duroc boars. By both peptide and PTM peptide quantification followed by statistical analyses, 167 differentially expressed proteins were identified from 1,745 proteins, and 283 differentially expressed phosphopeptides corresponding to 102 unique differentially phosphorylated proteins were measured from 1,140 identified phosphopeptides derived from 363 phosphorylated proteins. The representative results were validated by Western blots. Pathway enrichment analyses revealed that majority of differential expression proteins and differential phosphorylation proteins were primarily concerned with spermatogenesis, male gamete generation, sperm motility, energy metabolism, cilium morphogenesis, axonemal dynein complex assembly, sperm–egg recognition, and capacitation. Remarkably, axonemal dynein complex assembly related proteins, such as SMCP, SUN5, ODF1, AKAP3, and AKAP4 that play a key regulatory role in the sperm physiological functions, were significantly higher in Duroc spermatozoa than that of Yorkshire. Furthermore, phosphorylation of sperm-specific proteins, such as CABYR, ROPN1, CALM1, PRKAR2A, and PRKAR1A, participates in regulation of the boar sperm motility mainly through the cAMP/PKA signal pathway in different breeds, demonstrating that protein phosphorylation may be an important mechanism underlying the sperm diversity. Protein–protein interaction analysis revealed that the 14 overlapped proteins between differential expression proteins and differential phosphorylation proteins potentially played a key role in sperm development and motility of the flagellum, including the proteins ODF1, SMCP, AKAP4, FSIP2, and SUN5. Taken together, these physiologically and functionally differentially expressed proteins (DEPs) and differentially expressed phosphorylated proteins (DPPs) may constitute the proteomic backgrounds between the two different boar breeds. The validation will be performed to delineate the roles of these PTM proteins as modulators of Yorkshire and Duroc boar spermatozoa.

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Human sperm phosphoproteome reveals differential phosphoprotein signatures that regulate human sperm motility

Cited by 26 publications

References 29 publications

Integrated analysis of phosphoproteome and ubiquitylome in epididymal sperm of buffalo (Bubalus bubalis)

Integrated analysis of phosphoproteome and ubiquitylome in epididymal sperm of buffalo (Bubalus bubalis)

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation

Comparative Proteomics and Phosphoproteomics Analysis Reveal the Possible Breed Difference in Yorkshire and Duroc Boar Spermatozoa

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