Evolution of testis‐specific kinases <scp>TSSK</scp>1B and <scp>TSSK</scp>2 in primates

Shang, Peng; Hoogerbrugge, Jos W.; Baarends, Willy M.; Grootegoed, J. Anton

doi:10.1111/j.2047-2927.2012.00021.x

Cited by 19 publications

(22 citation statements)

References 52 publications

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“…Further experiments are needed to assay possible conserved functional roles [ 109 , 110 ] of the homologues identified here. Importantly, we found that our results were consistent with previous homology relationships described for 22q11.2DS genes (e.g., PRODH [ 111 ], UFD1L [ 112 ], DGCR6 [ 113 ], MED15 [ 114 ], TSSK2 [ 115 ], and TXNRD2 [ 116 ]). Using these methods, we identified multiple putative homologues for individual 22q11.2 deletion region genes in the zebrafish, possibly related to gene duplication [ 45 ].…”

Section: Discussionsupporting

confidence: 92%

Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms

Guna

Butcher

Bassett

2015

J Neurodevelop Disord

103

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Background22q11.2 deletion syndrome (22q11.2DS) is the most common micro-deletion syndrome. The associated 22q11.2 deletion conveys the strongest known molecular risk for schizophrenia. Neurodevelopmental phenotypes, including intellectual disability, are also prominent though variable in severity. Other developmental features include congenital cardiac and craniofacial anomalies. Whereas existing mouse models have been helpful in determining the role of some genes overlapped by the hemizygous 22q11.2 deletion in phenotypic expression, much remains unknown. Simple model organisms remain largely unexploited in exploring these genotype-phenotype relationships.MethodsWe first developed a comprehensive map of the human 22q11.2 deletion region, delineating gene content, and brain expression. To identify putative orthologs, standard methods were used to interrogate the proteomes of the zebrafish (D. rerio), fruit fly (D. melanogaster), and worm (C. elegans), in addition to the mouse. Spatial locations of conserved homologues were mapped to examine syntenic relationships. We systematically cataloged available knockout and knockdown models of all conserved genes across these organisms, including a comprehensive review of associated phenotypes.ResultsThere are 90 genes overlapped by the typical 2.5 Mb deletion 22q11.2 region. Of the 46 protein-coding genes, 41 (89.1 %) have documented expression in the human brain. Identified homologues in the zebrafish (n = 37, 80.4 %) were comparable to those in the mouse (n = 40, 86.9 %) and included some conserved gene cluster structures. There were 22 (47.8 %) putative homologues in the fruit fly and 17 (37.0 %) in the worm involving multiple chromosomes. Individual gene knockdown mutants were available for the simple model organisms, but not for mouse. Although phenotypic data were relatively limited for knockout and knockdown models of the 17 genes conserved across all species, there was some evidence for roles in neurodevelopmental phenotypes, including four of the six mitochondrial genes in the 22q11.2 deletion region.ConclusionsSimple model organisms represent a powerful but underutilized means of investigating the molecular mechanisms underlying the elevated risk for neurodevelopmental disorders in 22q11.2DS. This comparative multi-species study provides novel resources and support for the potential utility of non-mouse models in expression studies and high-throughput drug screening. The approach has implications for other recurrent copy number variations associated with neurodevelopmental phenotypes.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-015-9113-x) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms

Guna

Butcher

Bassett

2015

J Neurodevelop Disord

103

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“…ApTssk1 is grouped together with all mollusk Tssk1 genes of referred species, indicating they have a close genetic distance and may have evolved from the same ancestor (Shang et al 2013). These results strongly suggest that ApTssk1 is a member of the Tssk1 subfamily.…”

Section: Downloaded By [University Of Lethbridge] At 16:20 11 June 2016mentioning

confidence: 76%

“…Tssk1, a member of the highly conserved Tssk gene family widely reported to participate in spermatogenesis (Tanaka & Baba 2005), plays an important role in spermatid differentiation into morphologically mature spermatozoa in mammals (Shang et al 2009(Shang et al , 2013. Some studies have shown that Tssk1 is only expressed in the testis of humans and mice (visconti et al 2001;Li et al 2011;Yang et al 2012).…”

Section: Downloaded By [University Of Lethbridge] At 16:20 11 June 2016mentioning

confidence: 97%

“…It is important that each round of spermatids differentiates into morphologically mature spermatozoa during spermatogenesis (Sharpe 1994). The molecular mechanisms of spermatogenesis are to a large extent unknown; however, there is increasing evidence that the testis-specific serine kinase (Tssk) family plays an important role in the control of spermatogenesis (Bielke et al 1994;Shang et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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Characterization, expression, and functional analysis of testis-specific serine/threonine kinase 1 (Tssk1) in the pen shellAtrina pectinata

Kong

et al. 2016

Invertebrate Reproduction & Development

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Testis-specific serine/threonine kinase 1 (Tssk1) was named since its function was determined in mouse spermiogenesis. In our research, we cloned a homolog of the pen shell Atrina pectinata Tssk1, ApTssk1, and determined its expression characteristics at mRNA. The full length of ApTssk1 cDNA was 1517 bp, with an open reading frame of 1089 bp (58-1146), which encodes a peptide including 362 amino acids. The homologous analysis indicated that the deduced amino acid sequences of ApTssk1 shared a close identity with other reported Tssk1. In addition, the highly conserved fragment containing a serine/threonine protein kinase catalytic (S-TKc) domain was predicted to exist in ApTssk1. Results from the RT-qPCR display that ApTssk1 was only transcribed in the male gonad of A. pectinata, and was highest in the mature testis. Therefore, this study indicated that ApTssk1 might play a functional role during spermatogenesis in A. pectinata.

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“…A previous analysis of TSKS expression in Tssk1/Tssk2 mutant tubules has shown that TSSK1 or TSSK2 or both are required for the formation of the chromatoid body-derived ring and satellite structures as well as the correct localization of TSKS to these structures during spermiogenesis (Shang et al 2010). Also, recent analysis of the evolutionary history of the Tssk1 and Tssk2 genes in rodents and primates suggests that the two genes may have not completely overlapping functions (Shang et al 2013). One can thus envision a scenario where TSSK1 binds to and phosphorylates TSKS resulting in the localization of TSKS (and TSSK1) to specific puncta in the developing elongating spermatids, whereupon it binds to PPP1CC2, forming, at least transiently, a trimeric (or higher oligomer) complex.…”

Section: Ppp1cc2 Interacts With Tsks and Tssk1mentioning

confidence: 99%

PPP1CC2 can form a kinase/phosphatase complex with the testis-specific proteins TSSK1 and TSKS in the mouse testis

MacLeod¹,

Shang²,

Booth³

et al. 2014

Reproduction

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The mouse protein phosphatase gene Ppp1cc is essential for male fertility, with mutants displaying a failure in spermatogenesis including a widespread loss of post-meiotic germ cells and abnormalities in the mitochondrial sheath. This phenotype is hypothesized to be responsible for the loss of the testis-specific isoform PPP1CC2. To identify PPP1CC2-interacting proteins with a function in spermatogenesis, we carried out GST pull-down assays in mouse testis lysates. Amongst the identified candidate interactors was the testis-specific protein kinase TSSK1, which is also essential for male fertility. Subsequent interaction experiments confirmed the capability of PPP1CC2 to form a complex with TSSK1 mediated by the direct interaction of each with the kinase substrate protein TSKS. Interaction between PPP1CC2 and TSKS is mediated through an RVxF docking motif on the TSKS surface. Phosphoproteomic analysis of the mouse testis identified a novel serine phosphorylation site within the TSKS RVxF motif that appears to negatively regulate binding to PPP1CC2. Immunohistochemical analysis of TSSK1 and TSKS in the Ppp1cc mutant testis showed reduced accumulation to distinct cytoplasmic foci and other abnormalities in their distribution consistent with the loss of germ cells and seminiferous tubule disorganization observed in the Ppp1cc mutant phenotype. A comparison of Ppp1cc and Tssk1/2 knockout phenotypes via electron microscopy revealed similar abnormalities in the morphology of the mitochondrial sheath. These data demonstrate a novel kinase/phosphatase complex in the testis that could play a critical role in the completion of spermatogenesis.

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Evolution of testis‐specific kinases TSSK1B and TSSK2 in primates

Cited by 19 publications

References 52 publications

Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms

Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms

Characterization, expression, and functional analysis of testis-specific serine/threonine kinase 1 (Tssk1) in the pen shellAtrina pectinata

PPP1CC2 can form a kinase/phosphatase complex with the testis-specific proteins TSSK1 and TSKS in the mouse testis

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