Expression analysis of the human testis-specific serine/threonine kinase (TSSK) homologues. A TSSK member is present in the equatorial segment of human sperm

Hao, Zhonglin; Jha, Kula N.; Kim, Young Hwan; Vemuganti, Soumya; Westbrook, V. Anne; Chertihin, Olga; Markgraf, Karin; Flickinger, Charles J.; Coppola, Michael A.; Herr, John C.; Visconti, Pablo E.

doi:10.1093/molehr/gah052

Cited by 81 publications

(113 citation statements)

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“…Additionally, a group of genes that have generally been classified as ones involved in metabolism are significantly down-regulated in the testis upon loss of Taf7l and likely reflect both metabolic and spermatogenesis functions. These genes include the Tssk3 or Tsks testis-specific kinases (31,32), as well as Camk4, a protein kinase involved in phosphorylating protamines (33); Hk1 and GCK hexokinases involved in sperm glycolysis linked to motility (34); and Oaz3 (ornithine decarboxylase antizyme) that controls polyamines required for proper sperm formation (35,36) (Fig. 2D).…”

Section: Resultsmentioning

confidence: 99%

Taf7l cooperates with Trf2 to regulate spermiogenesis

Zhou

Grubisic

Zheng

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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TATA-binding protein (TBP)-associated factor 7l (Taf7l; a paralogue of Taf7) and TBP-related factor 2 (Trf2) are components of the core promoter complex required for gene/tissue-specific transcription of protein-coding genes by RNA polymerase II. Previous studies reported that Taf7l knockout (KO) mice exhibit structurally abnormal sperm, reduced sperm count, weakened motility, and compromised fertility. Here we find that continued backcrossing of Taf7l −/Y mice from N5 to N9 produced KO males that are essentially sterile. Genome-wide expression profiling by mRNA-sequencing analysis of wild-type (WT) and Taf7l −/Y (KO) testes revealed that Taf7l ablation impairs the expression of many postmeiotic spermatogenic-specific as well as metabolic genes. Importantly, histological analysis of testes revealed that Taf7l −/Y mice develop postmeiotic arrest at the first stage of spermiogenesis, phenotypically similar to Trf2 −/− mice, but distinct from Taf4b −/− mice. Indeed, we find that Taf7l and Trf2 coregulate postmeiotic genes, but none of Taf4b-regulated germ stem cell genes in testes. Genome-wide ChIP-sequencing studies indicate that TAF7L binds to promoters of activated postmeiotic genes in testis. Moreover, biochemical studies show that TAF7L associates with TRF2 both in vitro and in testis, suggesting that TAF7L likely cooperates directly with TRF2 at promoters of a subset of postmeiotic genes to regulate spermiogenesis. Our findings thus provide a previously undescribed mechanism for cell-type-specific transcriptional control involving an interaction between a "nonprototypic" core promoter recognition factor (Trf2) and an orphan TAF subunit (Taf7l) in mammalian testis-specific gene transcription.gene regulation | reproduction | RNA-seq | contraceptive medicine S permatogenesis is a cyclic process in which diploid spermatogonia differentiate into mature haploid spermatozoa. This process is mainly driven by two-pre-and postmeiotictranscription waves that are tightly controlled by testis-specific transcription factors. During the premeiotic transcription phase, individual spermatogonia are committed to differentiating into primary spermatocytes that later undergo two meiotic divisions to generate haploid round spermatids connected by intercellular cytoplasmic bridges (1-3). During the postmeiotic transcription phase of spermiogenesis, haploid round spermatids are sculptured into the elongated shape of mature spermatozoa. These latter stages are accompanied by dramatic biochemical and morphological changes, including major remodeling of chromatin with protamines substituting for somatic histones to tightly pack DNA into the sperm nucleus.Understanding the intricate mechanisms that control spermatogenesis has important implications for human health and reproduction. A key step in the regulation of spermatogenesis occurs at the level of transcription, starting with the use of distinct promoter elements (4) within uniquely reorganized chromatin (5) and driven by the action of several testis-specific transcription factors...

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Section: Resultsmentioning

confidence: 99%

Taf7l cooperates with Trf2 to regulate spermiogenesis

Zhou

Grubisic

Zheng

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been shown a 65 kDa protein, TSKS is a substrate of TSSK2 [26]. TSKS localizes predominantly to the centrioles of human sperm, however, TSSK2 is localized to the sperm neck, mid-piece of sperm tail, and to the equatorial segment (personal communication from John C Herr).…”

Section: Discussionmentioning

confidence: 99%

“…Mouse TSSK1 is abundant in germ cells during meiotic metaphase [25], while mouse TSSK2 is localized in the cytoplasm of male germ cells at late stage of spermatogenesis, and also in the flagella, acrosomal region of mature sperm, which is consistent with SPAG16L localization. In human sperm, TSSK2 was found in the neck region, equatorial region and midpiece of the flagella [20,25,26]. It has been shown that TSKS is a substrate for both TSSK1 and TSSK2 [19,21].…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of Sperm Axoneme Central Apparatus Protein SPAG16L by a Testis-specific Kinase, TSSK-2.

Zhang

Shen

Jones

et al. 2008

Biology of Reproduction

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Mammalian SPAG16L, the orthologue of Chlamydomonas Pf20, is an axoneme central apparatus protein necessary for flagellar motility. The SPAG16L protein sequence contains multiple potential phosphorylation sites and the protein was confirmed to be phosphorylated in vivo. A yeast-twohybrid screen identified the testis-specific kinase, TSSK2, to be a potential SPAG16L binding partner. SPAG16L and TSSK2 interactions were confirmed by co-immunoprecipitation of both proteins from testis extracts and cell lysates expressing these proteins, and their co-localization was also noted by confocal microscopy in CHO cells where they were co-expressed. TSSK2 associates with SPAG16L via its C terminal domain bearing WD repeats. The N-terminal domain containing a coiled coil motif does not associate with TSSK2. SPAG16L can be phosphorylated by TSSK2 in vitro. Finally, TSSK2 is absent or markedly reduced from the testes in most of the SPAG16L null mice. These data support the conclusion that SPAG16L is a TSSK2 substrate.

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“…Through phosphorylation of proteins, the testis-specific serine/threonine kinase (TSSK) family, which is expressed abundantly in the testis, is deeply involved in sperm differentiation, capacitation and fertilization [6][7][8][9][10][11]. Up to now, five members of this family have been identified, including TSSK1, TSSK2, TSSK3, TSSK4 and TSSK6.…”

Section: Introductionmentioning

confidence: 99%

“…TSSK6, also named small serine/threonine kinase, is expressed in elongating spermatids, and its coding gene, TSSK6, is mapped to 19p13.11, with only one exon encoding 273 amino acids [9,16]. A further study proposed that TSSK6 can phosphorylate histones H1, H2A, H2AX and H3, and can associate with heat shock protein HSP90 and HSC70 [16].…”

Section: Introductionmentioning

confidence: 99%