Tssk4 is essential for maintaining the structural integrity of sperm flagellum

Wang, Xiaoli; Wei, Youheng; Fu, Guolong; Li, Haitao; Saiyin, Hexige; Lin, Gang; Wang, Zhugang; Chen, Shi; Liu, Yu

doi:10.1093/molehr/gau097

Cited by 51 publications

(46 citation statements)

References 37 publications

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“…Furthermore, Tssk4 −/− mice are subfertile owing to disorganization of the midpiece–principal piece junction and significantly decreased sperm motility. 97, 98 TSSK4 and ODF2 can regulate each other through phosphorylation. 98 In addition, Sepp1 −/− and Tat1 −/− spermatozoa had structural defects similar to those described in Sept4 -null sperm, including thinning of the flagellum at the midpiece–principal piece junction and hairpin-like bending of the flagellum.…”

Section: Septin-based Organization Of the Annulusmentioning

confidence: 99%

“…97, 98 TSSK4 and ODF2 can regulate each other through phosphorylation. 98 In addition, Sepp1 −/− and Tat1 −/− spermatozoa had structural defects similar to those described in Sept4 -null sperm, including thinning of the flagellum at the midpiece–principal piece junction and hairpin-like bending of the flagellum. 99, 100, 101 However, the underlying mechanism of disorganization of the annulus in Sepp1 -null and Tat1 -null spermatozoa and their interaction with septins remain unknown.…”

Section: Septin-based Organization Of the Annulusmentioning

confidence: 99%

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The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

et al. 2016

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Male infertility due to abnormal spermatozoa has been reported in both animals and humans, but its pathogenic causes, including genetic abnormalities, remain largely unknown. On the other hand, contraceptive options for men are limited, and a specific, reversible and safe method of male contraception has been a long-standing quest in medicine. Some progress has recently been made in exploring the effects of spermatid-specifical genetic factors in controlling male fertility. A comprehensive search of PubMed for articles and reviews published in English before July 2016 was carried out using the search terms ‘spermiogenesis failure', ‘globozoospermia', ‘spermatid-specific', ‘acrosome', ‘infertile', ‘manchette', ‘sperm connecting piece', ‘sperm annulus', ‘sperm ADAMs', ‘flagellar abnormalities', ‘sperm motility loss', ‘sperm ion exchanger' and ‘contraceptive targets'. Importantly, we have opted to focus on articles regarding spermatid-specific factors. Genetic studies to define the structure and physiology of sperm have shown that spermatozoa appear to be one of the most promising contraceptive targets. Here we summarize how these spermatid-specific factors regulate spermiogenesis and categorize them according to their localization and function from spermatid head to tail (e.g., acrosome, manchette, head-tail conjunction, annulus, principal piece of tail). In addition, we emphatically introduce small-molecule contraceptives, such as BRDT and PPP3CC/PPP3R2, which are currently being developed to target spermatogenic-specific proteins. We suggest that blocking the differentiation of haploid germ cells, which rarely affects early spermatogenic cell types and the testicular microenvironment, is a better choice than spermatogenic-specific proteins. The studies described here provide valuable information regarding the genetic and molecular defects causing male mouse infertility to improve our understanding of the importance of spermatid-specific factors in controlling fertility. Although a male contraceptive ‘pill' is still many years away, research into the production of new small-molecule contraceptives targeting spermatid-specific proteins is the right avenue.

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Section: Septin-based Organization Of the Annulusmentioning

confidence: 99%

Section: Septin-based Organization Of the Annulusmentioning

confidence: 99%

The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

et al. 2016

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“…Heat shock protein 90 (HSP90) is essential for the stability of all TSSKs and for catalytic activation of TSSK2 and TSSK4 (Jha et al, 2013(Jha et al, , 2010. Tssk6-knockout (KO) and Tssk1/Tssk2 double KO mice exhibit male infertility (Shang et al, 2010;Spiridonov et al, 2005;Xu et al, 2008), whereas the targeted disruption of Tssk4 causes subfertility in male mice (Wang et al, 2015). Electron microscopy analysis of testis sections from Tssk6-KO mice indicates DNA condensation defects, and KO sperm have abnormal morphology, highly reduced motility and are incapable of fusing with zona pellucida-free eggs (Sosnik et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

TSSK6 is required for γH2AX formation and the histone-to-protamine transition during spermiogenesis

Jha

Tripurani

Johnson

2017

Journal of Cell Science

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Spermiogenesis includes transcriptional silencing, chromatin condensation and extensive morphological changes as spermatids transform into sperm. Chromatin condensation involves histone hyperacetylation, transitory DNA breaks, histone H2AX (also known as H2AFX) phosphorylation at Ser139 (γH2AX), and replacement of histones by protamines. Previously, we have reported that the spermatid protein kinase TSSK6 is essential for fertility in mice, but its specific role in spermiogenesis is unknown. Here, we show that TSSK6 expression is spatiotemporally coincident with γH2AX formation in the nuclei of developing mouse spermatids. RNAsequencing analysis demonstrates that genetic ablation of Tssk6 does not impact gene expression or silencing in spermatids. However, loss of TSSK6 blocks γH2AX formation, even though the timing and level of the transient DNA breaks is unaltered. Further, Tssk6-knockout sperm contained increased levels of histones H3 and H4, and protamine 2 precursor and intermediate(s) indicative of a defective histone-to-protamine transition. These results demonstrate that TSSK6 is required for γH2AX formation during spermiogenesis, and also link γH2AX to the histone-to-protamine transition and male fertility.

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“…Methylation in H3K9 was required for maintaining chromatin in repressed state [9], and it helps in maintaining some residual nucleosome core histones in paternal genome seen in sperm. Phosphorylation of H2A byTSSK6 is required for histone acetylation followed by condensation of chromatin [10,11]. May be DNA double strand breaks activate TSSK6 in late spermatids forming ɤH2AX foci required for replacement of histones with protamines [12].…”

Section: Various Histone Modifications During Spermiogenesismentioning

confidence: 99%

Understanding the Epigenetic Modifications in Sperm Genome

Beeram¹

2020

Innovations in Assisted Reproduction Technology

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Sperm genome condensation is mainly important as the genome expression should be repressed until it is fertilised with oocyte. In most of the mammals, protamines play an important role in genome condensation. In humans, histone variants were present in germ cells when compared with somatic cells. How successful replacement of histones by protamines occurs in most of the mammals is an interesting question. Little information is known about transition proteins that replace histones with protamines. Apart from condensation, which mechanisms prevent expression of X and Y chromosomes in sperm is to be studied. If exposed to genotoxic agents like Metosartan that damage testes should also be considered, in order for assisted reproductive technologies like in vitro fertilisation to succeed. Keywords: assisted reproductive technology (ART), intra cytoplasmic sperm injection (ICSI), invitro fertilisation (IVF), stem cell factor (SCF), protein dependent kinase (PDK), glial cell derived neurotropic factor (GDNF), post translational modification (PTM), chromatin assembly factor (CAF), testes specific serine/ threonine kinase 6 (TSSK6), nucleolar organising region (NOR), p-element induced wlmphy testes in drosophila (PIWI), a disintegrin and metalloprotease (ADAM)

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Tssk4 is essential for maintaining the structural integrity of sperm flagellum

Cited by 51 publications

References 37 publications

The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

TSSK6 is required for γH2AX formation and the histone-to-protamine transition during spermiogenesis

Understanding the Epigenetic Modifications in Sperm Genome

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