In-depth proteomic analysis of the human sperm reveals complex protein compositions

Wang, Gaigai; Guo, Yueshuai; Zhou, Tao; Shi, Xiaodan; Yu, Jun; Yang, Ye; Wu, Yibo; Wang, Jing; Liu, Mingxi; Chen, Xin; Tu, Wenjiao; Zeng, Yan; Jiang, Min; Li, Suying; Zhang, Pan; Zhou, Quan; Zheng, Bo; Yu, Chunmei; Zhou, Zuomin; Guo, Xuejiang; Sha, Jiahao

doi:10.1016/j.jprot.2012.12.008

Cited by 171 publications

(145 citation statements)

References 48 publications

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“…Proteomics has great potential for expanding the repertoire of clinical diagnostic tests of sperm in the infertility field. For example, reports of the entire human sperm proteome have increased our understanding of human sperm function (41,62), and comprehensive comparative studies between normal and abnormal spermatozoa have led to the discovery of novel peptides and metabolites that may be correlated with male infertility. With the novel antibodies we report here, clinicians can go a step further to examine whether impaired sperm function is due to altered PTMs.…”

Section: Discussionmentioning

confidence: 99%

“…DrugBank data have been used to annotate human sperm proteome and facilitate in silico drug target discovery by revealing that mitochondrial and ciliary proteins are the major drug targets (41). In a complementary approach, we therefore used WebGestalt software (42,43) to search for associations between known drugs or disease states using our sperm protein acetylation data set.…”

Section: Table I Synthesized Peptides Peptide Libraries and Peptide-mentioning

confidence: 99%

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Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

Diao

Wang

et al. 2015

Molecular & Cellular Proteomics

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Male infertility is a medical condition that has been on the rise globally. Lysine acetylation of human sperm, an essential posttranslational modification involved in the etiology of sperm abnormality, is not fully understood. Therefore, we first generated a qualified pan-anti-acetyllysine monoclonal antibody to characterize the global lysine acetylation of uncapacitated normal human sperm with a proteomics approach. With high enrichment ratios that were up to 31%, 973 lysine-acetylated sites that matched to 456 human sperm proteins, including 671 novel lysine acetylation sites and 205 novel lysine-acetylated proteins, were identified. These proteins exhibited conserved motifs XXXKYXXX, XXXKFXXX, and XXXKHXXX, were annotated to function in multiple metabolic processes, and were localized predominantly in the mitochondrion and cytoplasmic fractions. Between the uncapacitated and capacitated sperm, different acetylation profiles in regard to functional proteins involved in sperm capacitation, sperm-egg recognition, sperm-egg plasma fusion, and fertilization were observed, indicating that acetylation of functional proteins may be required during sperm capacitation. Bioinformatics analysis revealed association of acetylated proteins with diseases and drugs. Novel acetylation of voltage-dependent anion channel proteins was also found. With clinical sperm samples, we observed differed lysine acetyltransferases and lysine deacetylases expression between normal sperm and abnormal sperm of asthenospermia or necrospermia. Furthermore, with sperm samples impaired by epigallocatechin gallate to mimic asthenospermia, we observed that inhibition of sperm motility was partly through the blockade of voltage-dependent anion channel 2 Lys-74 acetylation combined with reduced ATP levels and mitochondrial membrane potential. Taken together, we obtained a qualified pananti-acetyllysine monoclonal antibody, analyzed the acetylproteome of uncapacitated human sperm, and revealed associations between functional protein acetylation and sperm functions. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

Section: Table I Synthesized Peptides Peptide Libraries and Peptide-mentioning

confidence: 99%

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

Diao

Wang

et al. 2015

Molecular & Cellular Proteomics

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“…Rab3-GAP1 and -2 were detected in a murine haploid germ cell proteome (79) and in the human sperm proteome. In the last one, a GEF for Rab3A was found too (80).…”

Section: Discussionmentioning

confidence: 99%

“…Baker et al (87) characterized the human sperm proteome and identified the presence of an ARF6 GAP of the BRAG family in male gametes. Recently, in-depth proteomic analysis of the human sperm revealed that ARF1, -4, -5, and -6 are present in the male gamete as well as different GAPs and GEFs for these GTPases (ACAP2, GIT1, AGAP1 and -3, ARF, GEF1 and -2) (80). The presence and function of these ARF6-GEFs have been extensively described in secretory cells, e.g.…”

Section: Discussionmentioning

confidence: 99%

ADP Ribosylation Factor 6 (ARF6) Promotes Acrosomal Exocytosis by Modulating Lipid Turnover and Rab3A Activation

Pelletán

Suhaiman

Vaquer

et al. 2015

Journal of Biological Chemistry

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Background: Sperm acrosomal exocytosis requires GTPases, SNAREs, and a complex lipid signaling. Results: Exocytic stimuli promote ARF6 activation, which accomplishes exocytosis by stimulating PLC and Rab3A. Conclusion: ARF6 induces acrosome calcium efflux and assembles the fusion machinery leading to membrane fusion. Significance: This study explores a novel molecular link between ARF6, PLC, and Rab3A and provides insight into the molecular mechanisms of exocytosis and reproduction.

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“…2) and is known to control intracellular calcium signals, cell metabolism and cell survival (for recent reviews, see Rizzuto et al (2012) and Patron et al (2013)). Proteomic data have confirmed that human sperm do possess MCU, as well as MCU regulator 1 , Wang et al 2013. However, mitochondrial uncoupling does not seem to significantly affect the calcium oscillations occurring in either progesterone-or nitric oxide-stimulated human sperm (Harper et al 2004, Machado-Oliveira et al 2008.…”

Section: C Signallingmentioning

confidence: 91%

Mitochondria functionality and sperm quality

Amaral¹,

Lourenço²,

Marques³

et al. 2013

Reproduction

433

332

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Although mitochondria are best known for being the eukaryotic cell powerhouses, these organelles participate in various cellular functions besides ATP production, such as calcium homoeostasis, generation of reactive oxygen species (ROS), the intrinsic apoptotic pathway and steroid hormone biosynthesis. The aim of this review was to discuss the putative roles of mitochondria in mammalian sperm function and how they may relate to sperm quality and fertilisation ability, particularly in humans. Although paternal mitochondria are degraded inside the zygote, sperm mitochondrial functionality seems to be critical for fertilisation. Indeed, changes in mitochondrial integrity/functionality, namely defects in mitochondrial ultrastructure or in the mitochondrial genome, transcriptome or proteome, as well as low mitochondrial membrane potential or altered oxygen consumption, have been correlated with loss of sperm function (particularly with decreased motility). Results from genetically engineered mouse models also confirmed this trend. On the other hand, increasing evidence suggests that mitochondria derived ATP is not crucial for sperm motility and that glycolysis may be the main ATP supplier for this particular aspect of sperm function. However, there are contradictory data in the literature regarding sperm bioenergetics. The relevance of sperm mitochondria may thus be associated with their role in other physiological features, particularly with the production of ROS, which in controlled levels are needed for proper sperm function. Sperm mitochondria may also serve as intracellular Ca 2C stores, although their role in signalling is still unclear.

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In-depth proteomic analysis of the human sperm reveals complex protein compositions

Cited by 171 publications

References 48 publications

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

ADP Ribosylation Factor 6 (ARF6) Promotes Acrosomal Exocytosis by Modulating Lipid Turnover and Rab3A Activation

Mitochondria functionality and sperm quality

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