ArticleAndrology2023
Testis-specific serine kinase 3 is required for sperm morphogenesis and male fertility.
Article in Andrology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Dynamic proteomics of Nasonia vitripennis pupal development reveals testis-specific regulation of new proteins (orphans) likely related to exo-α-sialidases.BMC genomics · 2026Article
- Article
- Dysregulated Kinase Expression in Teratozoospermia and Implications for Male Infertility: An Integrated Gene Expression Study.Journal of reproduction & infertility · 2025Article
- The novel HRD motif kinase SPE-60 is required for sperm development and motility in Caenorhabditis elegans.Scientific reports · 2025Article
- An allele-agnostic mutant-KRAS inhibitor suppresses tumor maintenance signals and reprograms tumor immunity in pancreatic cancer.Science translational medicine · 2025Article
- Identification of TSSK1 and TSSK2 as Novel Targets for Male Contraception.Biomolecules · 2025Article
- Article
- Article
- Large-scale CRISPR/Cas9 deletions within the WFDC gene cluster uncover gene functionality and critical roles in mammalian reproduction.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The role of HnrnpF/H as a driver of oligoteratozoospermia.iScience · 2024Article
- Characterization of sexual maturity-associated N6-methyladenosine in boar testes.BMC genomics · 2024Article
- Bringing proteomics to bear on male fertility: key lessons.Expert review of proteomics · 2024Review
- Chromosomal Inversions and the Demography of Speciation in Drosophila montana and Drosophila flavomontana.Genome biology and evolution · 2024Article
- Profiling of testis-specific or testis-predominant genes expressed in mouse male germ cell lines GC-1 and GC-2.Genes & genomics · 2024Article
- NaInternational journal of molecular sciences · 2023Review
- Molecular dissection and testing of PRSS37 function through LC-MS/MS and the generation of a PRSS37 humanized mouse model.Scientific reports · 2023Article
- Article
- Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility.Nature communications · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundThe importance of phosphorylation in sperm during spermatogenesis has not been pursued extensively. Testis-specific serine kinase 3 (Tssk3) is a conserved gene, but TSSK3 kinase functions and phosphorylation substrates of TSSK3 are not known.
objectiveThe goals of our studies were to understand the mechanism of action of TSSK3. MATERIALS AND
methodsWe analyzed the localization of TSSK3 in sperm, used CRISPR/Cas9 to generate Tssk3 knockout (KO) mice in which nearly all of the Tssk3 open reading frame was deleted (ensuring it is a null mutation), analyzed the fertility of Tssk3 KO mice by breeding mice for 4 months, and conducted phosphoproteomics analysis of male testicular germ cells.
resultsTSSK3 is expressed in elongating sperm and localizes to the sperm tail. To define the essential roles of TSSK3 in vivo, heterozygous (HET) or homozygous KO male mice were mated with wild-type females, and fertility was assessed over 4 months; Tssk3 KO males are sterile, whereas HET males produced normal litter sizes. The absence of TSSK3 results in disorganization of all stages of testicular seminiferous epithelium and significantly increased vacuolization of germ cells, leading to dramatically reduced sperm counts and abnormal sperm morphology; despite these histologic changes, Tssk3 null mice have normal testis size. To elucidate the mechanisms causing the KO phenotype, we conducted phosphoproteomics using purified germ cells from Tssk3 HET and KO testes. We found that proteins implicated in male infertility, such as GAPDHS, ACTL7A, ACTL9, and REEP6, showed significantly reduced phosphorylation in KO testes compared to HET testes, despite unaltered total protein levels.
conclusionsWe demonstrated that TSSK3 is essential for male fertility and crucial for phosphorylation of multiple infertility-related proteins. These studies and the pathways in which TSSK3 functions have implications for human male infertility and nonhormonal contraception.
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