Characterization of a novel gene, sperm‐tail‐associated protein (<i>Stap</i>), in mouse post‐meiotic testicular germ cells

Ohuchi, Jun; Arai, Toshio; Kon, Yasuhiro; Asano, Atsushi; Yamauchi, Hideto; Watanabe, Tomomasa

doi:10.1002/mrd.1041

Cited by 12 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because there are no known and characterized relatives, only very indirectly relevant information is available. Database searching on the basis of the unusually glutamate-rich amino acid composition reveals a similarity to intermediate filament proteins as well as to the sperm tail-associated proteins, Stap [26], or Spag5 [27], which is similar to the mitotic spindle protein Deepest and frog prothymosin-␣, which has a nuclear localization [28]. The analysis of secondary structure supports this by predicting long uninterrupted alpha-helical features, whose charge distribution would presuppose the formation of polymeric fibrils.…”

Section: Discussionmentioning

confidence: 83%

SPEER—A New Family of Testis-Specific Genes from the Mouse1

Spiess¹,

Walther²,

Müller³

et al. 2003

Biology of Reproduction

View full text Add to dashboard Cite

Differential cloning revealed a partial mRNA sequence expressed in the mouse testis, which on further molecular characterization proved to be a member of a new family of 14 transcribed genes. Six of the genes appear to be expressed pseudogenes. The remainder indicate an open reading frame of approximately 200-220 amino acids encoding proteins with a very high proportion of alpha helical secondary structure, comprising approximately 15% glutamate residues. Because of this property, the family has been named SPErm-associated glutamate (E)-Rich protein (SPEER). Three members were chosen for more detailed characterization: SPEER-1 (pseudogene), SPEER-2, and SPEER-4D. All three are expressed tissue specifically in the testis of mice, with only very weak expression evident in the rat testis but in no other species tested. Using reverse transcription-polymerase chain reaction (RT-PCR), all three transcripts can be detected also in the epididymis, presumably due to the presence of spermatozoa. All three transcripts are expressed to high levels in haploid germ cells at the spermatocyte-spermatid transition. SPEER-1 mRNA is present in the cytoplasm as a sense transcript, SPEER-2 appears to be made mostly as an antisense transcript, whereas SPEER-4D appears to be localized within a subcellular compartment as a conventional sense transcript. Codon usage analysis suggests that all but the pseudogenes can be expressed as protein, confirmed for SPEER-2 and SPEER-4D by in vitro transcription/translation. An antibody raised against a peptide region of SPEER-4D, which probably cross-reacts with other SPEER members, immunohistochemically stains the nuclei of early round spermatids. While there are no true homologies to other proteins in the genome databases, some motifs are present that suggest a relationship to nuclear matrix proteins, implying that the SPEER family is a new group of haploid sperm-specific nuclear factors.

show abstract

Section: Discussionmentioning

confidence: 83%

SPEER—A New Family of Testis-Specific Genes from the Mouse1

Spiess¹,

Walther²,

Müller³

et al. 2003

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…16 A previous study indicated that PMFBP1 was expressed in adult mouse testis, and more specifically, mRNA was highly expressed in round sperm and protein localized to the flagella of elongated sperm. 18 Rat Pmfbp1 (also known as ODF3 or Stap) is highly expressed in the testis of 6-to 21-week-old rats (https://www.ncbi.nlm.nih.gov/gene/171414). Our study was a combined investigation of human and mouse genetics, and based on our findings, suggests that PMFBP1 plays an important role in spermiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Biallelic mutations in PMFBP1 cause acephalic spermatozoa

Sha

Wang

et al. 2018

Clinical Genetics

View full text Add to dashboard Cite

The majority of men with defects in spermatogenesis remain undiagnosed. Acephalic spermatozoa is one of the diseases causing primary infertility. However, the causes underlying over half of affected cases remain unclear. Here, we report by whole‐exome sequencing the identification of homozygous and compound heterozygous truncating mutations in PMFBP1 of two unrelated individuals with acephalic spermatozoa. PMFBP1 was highly and specifically expressed in human and mouse testis. Furthermore, immunofluorescence staining in sperm from a normal control showed that PMFBP1 localizes to the head‐flagella junction region, and the absence of PMFBP1 was confirmed in patients harboring PMFBP1 mutations. In addition, we generated Pmfbp1 knock‐out (KO) mice, which we found recapitulate the acephalic sperm phenotype. Label‐free quantitative proteomic analysis of testicular sperm from Pmfbp1 KO and control mice showed 124 and 35 proteins, respectively, increased or decreased in sperm from KO mice compared to that found in control mice. Gene ontology analysis indicates that the biological process of Golgi vesicle transport was the most highly enriched in differentially expressed proteins, indicating process defects related to Golgi complex function may disturb formation of the head‐neck junction. Collectively, our data indicate that PMFBP1 is necessary for sperm morphology in both humans and mice, and that biallelic truncating mutations in PMFBP1 cause acephalic spermatozoa.

show abstract

“…Whole-exome sequence analysis of one of the brothers implicated a homozygous nonsense mutation (Table S2), c.1462C>T (p.Gln488*), in the coding region of PMFBP1 (GenBank: NM_031293.2), a gene specifically expressed in testis that encodes a sperm tail-associated protein (STAP), but its complete function had not yet been determined. 25 To determine whether PMFBP1 is another acephalic spermatozoa syndrome-related gene, similar to SUN5 that we recently reported, we Sanger sequenced PMFBP1 in ten additional infertile men with acephalic spermatozoa syndrome and without SUN5 mutations. 18 1A and 1B, Tables S1 and S2, see Supplemental Note).…”

Section: Pmfbp1 and Acephalic Spermatozoa Syndromementioning

confidence: 96%

Mutations in PMFBP1 Cause Acephalic Spermatozoa Syndrome

Zhu

Liu

Wang

et al. 2018

The American Journal of Human Genetics

121

View full text Add to dashboard Cite

Acephalic spermatozoa syndrome is a severe teratozoospermia that leads to male infertility. Our previous work showed that biallelic SUN5 mutations are responsible for acephalic spermatozoa syndrome in about half of affected individuals, while pathogenic mechanisms in the other individuals remain to be elucidated. Here, we identified a homozygous nonsense mutation in the testis-specific gene PMFBP1 using whole-exome sequencing in a consanguineous family with two infertile brothers with acephalic spermatozoa syndrome. Sanger sequencing of PMFBP1 in ten additional infertile men with acephalic spermatozoa syndrome and without SUN5 mutations revealed two homozygous variants and one compound heterozygous variant. The disruption of Pmfbp1 in male mice led to infertility due to the production of acephalic spermatozoa and the disruption of PMFBP1's cooperation with SUN5 and SPATA6, which plays a role in connecting sperm head to the tail. PMFBP1 mutation-associated male infertility could be successfully overcome by intracytoplasmic sperm injection (ICSI) in both mouse and human. Thus, mutations in PMFBP1 are an important cause of infertility in men with acephalic spermatozoa syndrome.

show abstract

Characterization of a novel gene, sperm‐tail‐associated protein (Stap), in mouse post‐meiotic testicular germ cells

Cited by 12 publications

References 37 publications

SPEER—A New Family of Testis-Specific Genes from the Mouse1

SPEER—A New Family of Testis-Specific Genes from the Mouse1

Biallelic mutations in PMFBP1 cause acephalic spermatozoa

Mutations in PMFBP1 Cause Acephalic Spermatozoa Syndrome

Contact Info

Product

Resources

About