Paper 1. Sosnik_et_al-1

Paper 1. Sosnik_et_al-1 - Research Article 2741 Tssk6 is...

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2741 Research Article Introduction Spermatogenesis in the testis is responsible for the production of functional spermatozoa; this process is divided into three stages. Initially, spermatogenesis involves a proliferative phase in which spermatogonia undergo mitotic divisions and generate spermatocytes; second, the meiotic phase is responsible for generating haploid spermatids; finally, the postmeiotic phase, known as spermiogenesis, is characterized by a profound morphological differentiation that starts in the haploid spermatid and culminates in morphologically mature sperm. Spermiogenesis includes the formation of the acrosome, condensation and reorganization of the chromatin, elongation and species-specific reshaping of the cell, and the assembly of the flagellum (Sharpe, 1994). Although the molecular mechanisms regulating these events are poorly understood, it is known that, during spermiogenesis, there are significant changes in both transcription (Hecht, 1988) and translation (Hake et al., 1990). Some of the proteins translated in the haploid spermatid will remain in the morphologically mature sperm after it leaves the testis. Therefore, proteins that are synthesized during spermiogenesis might be necessary for spermatid differentiation and/or for sperm function during fertilization. Given the importance of phosphorylation events in the regulation of cellular signaling processes and differentiation, it is not surprising that several protein kinases have been shown to be involved in spermatogenesis (Sassone-Corsi, 1997). Some of them are exclusively expressed in germ cells or in the testis (Jinno et al., 1993; Walden and Cowan, 1993; Nayak et al., 1998; Toshima et al., 1998; Tseng et al., 1998; Shalom and Don, 1999; Toshima et al., 1999). Among them, the testis-specific serine kinase (Tssk) gene family is postmeiotically expressed in male germ cells (Bielke et al., 1994; Kueng et al., 1997; Visconti et al., 2001). The conserved testicular expression pattern of Tssk genes as well as the importance of phosphorylation in signaling processes strongly suggest that kinases of the Tssk family have a role(s) in germ-cell differentiation and/or sperm function. The importance of Tssk(s) has been recently demonstrated by phenotypic analysis of Tssk6 (also known as Sstk) knock-out (KO) mice ( Mus musculus ) (Spiridonov et al., 2005). Male, but not female, Tssk6- null mice are infertile without exhibiting somatic abnormalities. In addition, recently, two groups reported the phenotype of the Tssk1 and Tssk2 double KO. Although one group reported lack of founders due to haploinsufficiency (Xu et al., 2008), the second group was able to obtain Tssk1 - and Tssk2- null mice, and showed that these mice were sterile and no other defects were observed (Shang et al., 2007). Taken together, these reports suggest that, similar to Tssk6, Tssk1 and/or Tssk2 are essential for spermiogenesis and/or sperm function. Tssk6
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Paper 1. Sosnik_et_al-1 - Research Article 2741 Tssk6 is...

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