Translocation of Tektin 3 to the equatorial segment of heads in bull spermatozoa exposed to dibutyryl cAMP and calyculin A

Tsukamoto, Mariko; Hiyama, Erina; Hirotani, Karen; Gotoh, Takafumi; Inai, Tetsuichiro; Iida, Hiroshi

doi:10.1002/mrd.22763

Cited by 4 publications

(1 citation statement)

References 58 publications

(99 reference statements)

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“…These downregulated proteins make contact with each other to develop complex interacting networks, which widely participate in vesicle formation and transport, sperm head organisation, fertilisation, acrosome assembly and sperm axoneme assembly (figure 5C). According to the literature, nine of these proteins, including ZPBP1, SPACA1, SPINK2, CSNK2A2, DPY19L2, CCDC62, CCIN, TEKT2 and TEKT3, are explicitly related to the formation of the acrosome 17–24. Additionally, H1-7 is associated with spermatid nucleus differentiation25; SPAM126and ACR27 are involved with the binding of sperm to zona pellucida and TEKT5 participates in sperm flagella 28.…”

Section: Resultsmentioning

confidence: 99%

FSIP2plays a role in the acrosome development during spermiogenesis

Zheng

Wang

et al. 2022

J Med Genet

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BackgroundLoss-of-function mutations in FSIP2 result in multiple morphological abnormalities of the flagella in humans and mice. Intriguingly, a recent study found that FSIP2 might regulate the expression of acrosomal proteins, indicating that Fsip2 might be involved in acrosome development in mice. However, whether FSIP2 also function in acrosome biogenesis in humans is largely unknown, and the underlying mechanism of which is unexplored.ObjectiveOur objective was to reveal potential function of FSIP2 in regulating sperm acrosome formation.MethodsWe performed whole exome sequencing on four asthenoteratozoospermic patients. Western blot analysis and immunofluorescence staining were conducted to assess the protein expression of FSIP2. Proteomics approach, liquid chromatography-tandem mass spectrometry and co-immunoprecipitation were implemented to clarify the molecules in acrosome biogenesis regulated by FSIP2.ResultsBiallelic FSIP2 variants were identified in four asthenoteratozoospermic individuals. The protein expression of MUT-FSIP2 was sharply decreased or absent in vitro or in vivo. Interestingly, aside from the sperm flagellar defects, the acrosomal hypoplasia was detected in numerous sperm from the four patients. FSIP2 co-localised with peanut agglutinin in the acrosome during spermatogenesis. Moreover, FSIP2 interacted with proteins (DPY19L2, SPACA1, HSP90B1, KIAA1210, HSPA2 and CLTC) involved in acrosome biogenesis. In addition, spermatozoa from patients carrying FSIP2 mutations showed downregulated expression of DPY19L2, ZPBP, SPACA1, CCDC62, CCIN, SPINK2 and CSNK2A2.ConclusionOur findings unveil that FSIP2 might involve in sperm acrosome development, and consequently, its mutations might contribute to globozoospermia or acrosomal aplasia. We meanwhile first uncover the potential molecular mechanism of FSIP2 regulating acrosome biogenesis.

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Section: Resultsmentioning

confidence: 99%

FSIP2plays a role in the acrosome development during spermiogenesis

Zheng

Wang

et al. 2022

J Med Genet

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Bi-allelic human TEKT3 mutations cause male infertility with oligoasthenoteratozoospermia owing to acrosomal hypoplasia and reduced progressive motility

Liu

Meng

et al. 2023

Human Molecular Genetics

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Oligoasthenoteratozoospermia (OAT) can result in male infertility due to reduced sperm motility and abnormal spermatozoan morphology. The Tektins are a family of highly conserved filamentous proteins expressed in the axoneme and associated structures in many different metazoan species. Earlier studies on mice identified Tektin3 (Tekt3) as a testis-enriched gene, and knockout of Tekt3 resulted in asthenozoospermia in the mice. Here, whole exome sequencing of 100 males with asthenozoospermia from unrelated families was performed, followed by Sanger sequencing, leading to the identification of TEKT3 as a candidate gene in two of these patients and their associated family members. In total, three mutations in the TEKT3 gene were identified in both these patients, including one homozygous deletion–insertion mutation (c.543_547delinsTTGAT: p.Glu182*) and one compound heterozygous mutation (c.[548G > A]; [752A > C], p.[(Arg183Gln)]; [(Gln251Pro)]). Both of these mutations resulted in the complete loss of TEKT3 expression. The patients were both found to produce sperm that, although they showed no apparent defects in the flagellar structure, had reduced progressive motility. In contrast to mice, most sperm from these two patients exhibited acrosomal hypoplasia, although this did not prevent the use of the sperm for in vitro fertilization through an ICSI approach. TEKT3 was found to bind to other TEKT proteins, suggesting that these proteins form a complex within human spermatozoa. Overall, these results suggest that a loss of TEKT3 function can contribute to OAT incidence in humans. TEKT3 deficiencies can reduce sperm motility and contribute to severe acrosomal hypoplasia in spermatozoa, compromising their normal function.

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