|Ana Maria Salicioni
Assistant Professor of Veterinary and Animal Science, University of Massachusetts
Ph.D.: University of San Luis, Argentina
Molecular Mechanisms Responsible for Sperm Function. Role of Testis-Specific Kinases in Male Fertility and as Targets for Contraception
Our research is focused on understanding the cell signaling events conducive to sperm capacitation as well as the mechanism(s) by which the capacitated sperm is then able to induce activation and to trigger development in mammalian eggs, ultimately leading to a successful development of the embryo. As part of this task, we are interested in identifying the molecule(s) involved in these events in male germ cells, among which we count the novel family of testis-specific serine protein kinases (TSSKs). The TSSK protein family belongs to the AMPK kinase branch in the CAMK group, and is composed of six members, TSSK1 through TSSK6; whether Tssk5 has all the domains required to be an active kinase has not yet been determined. Using an array of TSSK specific antibodies, we have investigated the localization of TSSKs in mouse and human sperm and demonstrated that TSSK1, TSSK2, TSSK4 and TSSK6 are present in mature sperm (Li et al., 2011). Our studies have provided further support to previous observations indicating that TSSK family members display a different cellular localization, thus suggesting a non-redundant role for these protein kinases. The restricted expression of TSSKs during differentiation of spermatids in the testis, as well as the importance of phosphorylation in signaling pathways, has lead to the prediction that TSSK(s) have an important role(s) in germ cell differentiation and/or sperm function. This prediction has been recently confirmed by the sterile phenotype of the Tssk6 knock-out mice (Spiridonov et al., 2005, Sosnik et al., 2009)and of the double Tssk1 and Tssk2 KO (Xu et al., 2008; Shang et al., 2010). Despite these new discoveries, the specific function and mode of action of Tssks in male reproduction has yet to be determined.
Battistone MA, Da Ros VG, Salicioni AM, Navarrete FA, Krapf D, Visconti PE, Cuasnicú PS. 2013. Functional human sperm capacitation requires both bicarbonate-dependent PKA activation and down-regulation of Ser/Thr phosphatases by Src family kinases.. Mol Hum Reprod.
Jha KN, Coleman AR, Wong L, Salicioni AM, Howcroft E, Johnson GR. 2013. Heat shock protein 90 functions to stabilize and activate the testis-specific serine/threonine kinases, a family of kinases essential for male fertility.. J Biol Chem. 288(23):16308-20.
Salicioni AM, Romano FB, Visconti PE. 2012. Testis-Specific Kinases in male Fertility and as Targets for Contraception. American Pharmaceutical Review. 15(5).
Porambo JR, Salicioni AM, Visconti PE, Platt MD. 2012. Sperm phosphoproteomics: historical perspectives and current methodologies.. Expert Rev Proteomics. 9(5):533-48.
Li Y, Sosnik J, Brassard L, Reese M, Spiridonov NA, Bates TC, Johnson GR, Anguita J, Visconti PE, Salicioni AM. 2011. Expression and localization of five members of the testis-specific serine kinase (Tssk) family in mouse and human sperm and testis. Molec Hum Reprod. 17(1):42-56.
Krapf D, Arcelay E, Wertheimer EV, Sanjay A, Pilder SH, Salicioni AM, Visconti PE. 2010. Inhibition of Ser/Thr phosphatases induces capacitation-associated signaling in the presence of Src kinase inhibitors.. The Journal of biological chemistry. 285(11):7977-85
O'Brien ED, Salicioni AM, Cabada MO, Arranz SE. 2010. Vitellogenesis in Bufo arenarum: identification, characterization and immunolocalization of high molecular mass lipovitellin during oogenesis.. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.
Platt MD, Salicioni AM, Hunt DF, Visconti PE. 2009. Use of differential isotopic labeling and mass spectrometry to analyze capacitation-associated changes in the phosphorylation status of mouse sperm proteins.. Journal of proteome research. 8(3):1431-40.
Wertheimer EV, Salicioni AM, Liu W, Trevino CL, Chavez J, Hernández-González EO, Darszon A, Visconti PE. 2008. Chloride Is essential for capacitation and for the capacitation-associated increase in tyrosine phosphorylation.. The Journal of biological chemistry. 283(51):35539-50.
Arcelay E, Salicioni AM, Wertheimer E, Visconti PE. 2008. Identification of proteins undergoing tyrosine phosphorylation during mouse sperm capacitation.. The International journal of developmental biology. 52(5-6):463-72.
Yoon S-Y, Jellerette T, Salicioni AM, Lee HC, Yoo M-S, Coward K, Parrington J, Grow D, Cibelli JB, Visconti PE et al.. 2008. Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development.. The Journal of clinical investigation.
Salicioni AM, Platt MD, Wertheimer EV, Arcelay E, Allaire A, Sosnik J, Visconti PE. 2007. Signalling pathways involved in sperm capacitation.. Society of Reproduction and Fertility supplement.
Jha KN, Salicioni AM, Arcelay E, Chertihin O, Kumari S, Herr JC, Visconti PE. 2006. Evidence for the involvement of proline-directed serine/threonine phosphorylation in sperm capacitation.. Molecular human reproduction. 12(12):781-9.
Gaultier A, Salicioni AM, Arandjelovic S, Gonias SL. 2006. Regulation of the composition of the extracellular matrix by low density lipoprotein receptor-related protein-1: activities based on regulation of mRNA expression.. The Journal of biological chemistry. 281(11):7332-40.
Salicioni AM, Gaultier A, Brownlee C, Cheezum MK, Gonias SL. 2004. Low density lipoprotein receptor-related protein-1 promotes beta1 integrin maturation and transport to the cell surface.. The Journal of biological chemistry. 279(11):10005-12.
Gonias SL, Wu L, Salicioni AM. 2004. Low density lipoprotein receptor-related protein: regulation of the plasma membrane proteome.. Thrombosis and haemostasis. 91(6):1056-64.
Salicioni AM, Mizelle KS, Loukinova E, Mikhailenko I, Strickland DK, Gonias SL. 2002. The low density lipoprotein receptor-related protein mediates fibronectin catabolism and inhibits fibronectin accumulation on cell surfaces.. The Journal of biological chemistry. 277(18):16160-6.
Ma Z, Thomas KS, Webb DJ, Moravec R, Salicioni AM, Mars WM, Gonias SL. 2002. Regulation of Rac1 activation by the low density lipoprotein receptor-related protein.. The Journal of cell biology. 159(6):1061-70.
Guerreiro Da Silva ID, Hu YF, Russo IH, Ao X, Salicioni AM, Yang X, Russo J. 2000. S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo.. International journal of oncology. 16(2):231-40.
Salicioni AM, Xi M, Vanderveer LA, Balsara B, Testa JR, Dunbrack RL, Godwin AK. 2000. Identification and structural analysis of human RBM8A and RBM8B: two highly conserved RNA-binding motif proteins that interact with OVCA1, a candidate tumor suppressor.. Genomics. 69(1):54-62.