Acetylated α-tubulin is reduced in individuals with poor sperm motility

Bhagwat, Shweta; Dalvi, Veena; Chandrasekhar, Darshan; Matthew, Tinsu; Acharya, Kshitish K.; Gajbhiye, Rahul; Kulkarni, Vijay; Sonawane, Shobha; Ghosalkar, Manish; Parte, Priyanka

doi:10.1016/j.fertnstert.2013.09.016

Cited by 66 publications

(48 citation statements)

References 36 publications

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“…Tuba8 was absent from the immature sperm shed into the lumen of the tubules; this contrasts to a recent report in which TUBA8 was described in the flagella of human spermatozoa, and was reduced in asthenozoospermia, at the RNA and protein level [26]. Immunocytochemistry on sperm from the mouse model did label the flagella, but failed to detect a difference between control and knockout mice, suggesting this staining was not Tuba8-specific (S6 Fig, S1 Appendix).…”

Section: Resultscontrasting

confidence: 84%

A tubulin alpha 8 mouse knockout model indicates a likely role in spermatogenesis but not in brain development

et al. 2017

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Tubulin alpha 8 (Tuba8) is the most divergent member of the highly conserved alpha tubulin family, and uniquely lacks two key post-translational modification sites. It is abundantly expressed in testis and muscle, with lower levels in the brain. We previously identified homozygous hypomorphic TUBA8 mutations in human subjects with a polymicrogyria (PMG) syndrome, suggesting its involvement in development of the cerebral cortex. We have now generated and characterized a Tuba8 knockout mouse model. Homozygous mice were confirmed to lack Tuba8 protein in the testis, but did not display PMG and appeared to be neurologically normal. In response to this finding, we re-analyzed the human PMG subjects using whole exome sequencing. This resulted in identification of an additional homozygous loss-of-function mutation in SNAP29, suggesting that SNAP29 deficiency, rather than TUBA8 deficiency, may underlie most or all of the neurodevelopmental anomalies in these subjects. Nonetheless, in the mouse brain, Tuba8 specifically localised to the cerebellar Purkinje cells, suggesting that the human mutations may affect or modify motor control. In the testis, Tuba8 localisation was cell-type specific. It was restricted to spermiogenesis with a strong acrosomal localization that was gradually replaced by cytoplasmic distribution and was absent from spermatozoa. Although the knockout mice were fertile, the localisation pattern indicated that Tuba8 may have a role in spermatid development during spermatogenesis, rather than as a component of the mature microtubule-rich flagellum itself.

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Section: Resultscontrasting

confidence: 84%

A tubulin alpha 8 mouse knockout model indicates a likely role in spermatogenesis but not in brain development

et al. 2017

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“…Lysine acetylation of sperm tubulins is essential for sperm motility, and a recent publication showed an association between acetylated ␣-tubulin isoforms (TUBA3C and TUBA4A) and asthenospermia (27). We also identified site-specific acetylation of these ␣-tubulin isoforms in the current study (supplemental Table 10).…”

Section: Discussionsupporting

confidence: 69%

“…Protein acetylation can modulate proteasomal degradation of core histones (25) and axonemal microtubule construction (26,27) consistent with findings that poor sperm motility and male infertility are associated with perturbed ␣-tubulin acetylation (27). Previous in vitro studies also showed that a histone acetylase inhibitor causes spermatid apoptosis, down-regulation of histone acetylation, and a cease in translation in advance (29).…”

supporting

confidence: 82%

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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“…This motif was detected exclusively in the G1 set of the tubulin proteins validated as SUMO targets (Table 2). Many studies (Wloga et al, 2010; Bhagwat et al, 2014) suggest that acetylated tubulin may affect sperm mobility. In addition, we noted that 18% of the predicted targets contain the SUMO-Interacting motifs type SIM Type β.…”

Section: Discussionmentioning

confidence: 99%

Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa

et al. 2017

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Mature spermatozoa have highly condensed DNA that is essentially silent both transcriptionally and translationally. Therefore, post translational modifications are very important for regulating sperm motility, morphology, and for male fertility in general. Protein sumoylation was recently demonstrated in human and rodent spermatozoa, with potential consequences for sperm motility and DNA integrity. We examined the expression and localization of small ubiquitin-related modifier-1 (SUMO-1) in the sperm of water buffalo (Bubalus bubalis) using immunofluorescence analysis. We confirmed the expression of SUMO-1 in the acrosome. We further found that SUMO-1 was lost if the acrosome reaction was induced by calcium ionophore A23187. Proteins modified or conjugated by SUMO-1 in water buffalo sperm were pulled down and analyzed by mass spectrometry. Sixty proteins were identified, including proteins important for sperm morphology and motility, such as relaxin receptors and cytoskeletal proteins, including tubulin chains, actins, and dyneins. Forty-six proteins were predicted as potential sumoylation targets. The expression of SUMO-1 in the acrosome region of water buffalo sperm and the identification of potentially SUMOylated proteins important for sperm function implicates sumoylation as a crucial PTM related to sperm function.

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Acetylated α-tubulin is reduced in individuals with poor sperm motility

Cited by 66 publications

References 36 publications

A tubulin alpha 8 mouse knockout model indicates a likely role in spermatogenesis but not in brain development

A tubulin alpha 8 mouse knockout model indicates a likely role in spermatogenesis but not in brain development

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

Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa

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