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Prothymosin alpha expression and localization during the spermatogenesis of Danio rerio

  • Paolo Pariante (a1), Raffaele Dotolo (a2), Massimo Venditti (a2), Diana Ferrara (a2), Aldo Donizetti (a3), Francesco Aniello (a3) and Sergio Minucci (a1)...

Summary

Prothymosin α (PTMA) is a highly acidic, intrinsically disordered protein, which is widely expressed and conserved throughout evolution; its uncommon features are reflected by its involvement in a variety of processes, including chromatin remodelling, transcriptional regulation, cell proliferation and death, immunity. PTMA has also been implicated in spermatogenesis: during vertebrate germ cell progression in the testis the protein is expressed in meiotic and post-meiotic stages, and it is associated with the acrosome system of the differentiating spermatids in mammals. Then, it finally localizes on the inner acrosomal membrane of the mature spermatozoa, suggesting its possible role in both the maturation and function of the gametes. In the present work we studied PTMA expression during the spermatogenesis of the adult zebrafish, a species in which two paralogs have been described. Our data show that ptma transcripts are expressed in the testis, and localize in meiotic and post-meiotic germ cells, namely spermatocytes and spermatids. Consistently, the protein is expressed in spermatocytes, spermatids, and spermatozoa: its initial perinuclear distribution is extended to the chromatin region during cell division and, in haploid phases, to the cytoplasm of the developing and final gametes. The nuclear localization in the acrosome-lacking spermatozoa suggests a role for PTMA in chromatin remodelling during gamete differentiation. These data further provide a compelling starting point for the study of PTMA functions during vertebrate fertilization.

Copyright

Corresponding author

All correspondence to: Paolo Pariante or Sergio Minucci. Dipartimento di Medicina Sperimentale, Seconda Università di Napoli. 80138, Napoli, Italy. Tel: +39 0815665829. E-mail: paolo.pariante@unina2.it or sergio.minucci@unina2.it

References

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Aniello, F., Branno, M., De Rienzo, G., Ferrara, D., Palmiero, C. & Minucci, S. (2002). First evidence of prothymosin alpha in a non-mammalian vertebrate and its involvement in the spermatogenesis of the frog Rana esculenta . Mech. Dev. 110, 213–7.
Baxevanis, C.N., Thanos, D., Reclos, G.J., Anastasopoulos, E., Tsokos, G.C., Papamatheakis, J. & Papamichail, M. (1992). Prothymosin alpha enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation. J. Immunol. 148, 1979–84.
Billard, R. (1990). Spermatogenesis in teleost fish. In Marshall's Physiology of Reproduction. Reproduction in Males, vol. 2 (ed. Lamming, G.E.), pp. 183212. Edinburgh: Churchill Livingston.
Carrell, D.T. (2011). Epigenetic marks in zebrafish sperm: insights into chromatin compaction., maintenance of pluripotency., and the role of the paternal genome after fertilization. Asian J. Androl. 13, 620–1.
Clinton, M., Frangou-Lazaridis, M., Panneerselvam, C. & Horecker, B.L. (1989). Prothymosin alpha and parathymosin: mRNA and polypeptide levels in rodent tissues. Arch. Biochem. Biophys. 269, 256–63.
De Rienzo, G., Di Sena, R., Ferrara, D., Palmiero, C., Chieffi Baccari, G. & Minucci, S. (2002). Temporal and spatial localization of prothymosin alpha transcript in the Harderian gland of the frog, Rana esculenta . J. Exp. Zool. 292, 633–9.
Dominguez, F., Magdalena, C., Cancio, E., Roson, E., Paredes, J., Loidi, L., Zalvide, J., Fraga, M., Forteza, J. & Regueiro, B.J. (1993). Tissue concentrations of prothymosin alpha: a novel proliferation index of primary breast cancer. Eur. J. Cancer 29A, 893–7.
Donizetti, A., Liccardo, D., Esposito, D., Del Gaudio, R., Locascio, A., Ferrara, D., Minucci, S., Aniello, F. (2008). Differential expression of duplicated genes for prothymosin alpha during zebrafish development. Dev. Dyn. 237, 1112–8.
Dosil, M., Freire, M. & Gómez-Márquez, J. (1990). Tissue-specific and differential expression of prothymosin alpha gene during rat development. FEBS Lett. 269, 373–6.
Enkemann, S.A., Ward, R.H., Trumbore, M.W. & Berger, S.L. (2000a). Functional discontinuities in prothymosin alpha caused by caspase cleavage in apoptotic cells. J. Cell. Physiol. 182, 256–68.
Enkemann, S.A., Ward, R.D. & Berger, S.L. (2000b). Mobility within the nucleus and neighboring cytosol is a key feature of prothymosin-alpha. J. Histochem. Cytochem. 48, 1341–55.
Ferrara, D., Palmiero, C., Branno, M., Pierantoni, R., Minucci, S (2004). Testicular activity of Mos in the frog, Rana esculenta: a new role in spermatogonial proliferation. Biol. Reprod. 70, 1782–9. .
Ferrara, D., Izzo, G., Liguori, L., d’Istria, M., Aniello, F. & Minucci, S. (2009). Evidence for the involvement of prothymosin alpha in the spermatogenesis of the frog Rana esculenta . J. Exp. Zool. A Ecol. Genet. Physiol. 311, 110.
Ferrara, D., Izzo, G., Pariante, P., Donizetti, A., d’Istria, M., Aniello, F. & Minucci, S. (2010). Expression of prothymosin alpha in meiotic and post-meiotic germ cells during the first wave of rat spermatogenesis. J. Cell. Physiol. 224, 362–8.
Ferrara, D., Pariante, P., Di Matteo, L., Serino, I., Oko, R. & Minucci, S. (2013). First evidence of prothymosin α localization in the acrosome of mammalian male gametes. J. Cell. Physiol. 228, 1629–37.
Frangou-Lazaridis, M., Clinton, M., Goodall, G.J. & Horecker, B.L. (1988). Prothymosin alpha and parathymosin: amino acid sequences deduced from the cloned rat spleen cDNAs. Arch. Biochem. Biophys. 263, 305–10.
Gast, K., Damaschun, H., Eckert, K., Schulze-Forster, K., Maurer, H.R., Müller-Frohne, M., Zirwer, D., Czarnecki, J. & Damaschun, G. (1995). Prothymosin alpha: a biologically active protein with random coil conformation. Biochemistry 34, 13211–8.
Grier, H.J. (1993). Comparative organization of Sertoli cells including the Sertoli cell barrier. In The Sertoli Cell (eds Russell, L.D. & Griswold, M.D.), pp. 704–30. Clearwater, Florida: Cache River Press.
Hannappel, E. & Huff, T. (2003). The thymosins. Prothymosin alpha, parathymosin, and beta-thymosins: structure and function. Vitam. Horm. 66, 257–96.
Haritos, A.A., Goodall, G.J. & Horecker, B.L. (1984a). Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. Proc. Natl. Acad. Sci. USA 81, 1008–11.
Haritos, A.A., Tsolas, O. & Horecker, B.L. (1984b). Distribution of prothymosin alpha in rat tissues. Proc. Natl. Acad. Sci. USA 81, 1391–3.
Hirai, A. (1988). Fine structure of the micropyles of pelagic eggs of some marine fishes. Jap. J. Ichthyol. 35, 351–7.
Huszno, J. & Klag, J. (2012). The reproductive cycle in the male gonads of Danio rerio (Teleostei, Cyprinidae). Stereological analysis. Micron 43, 666–72.
Jiang, X., Kim, H.E., Shu, H., Zhao, Y., Zhang, H., Kofron, J., Donnelly, J., Burns, D., Ng, S.C., Rosenberg, S. & Wang, X. (2003). Distinctive role of PHAP proteins and prothymosin-alpha in a death regulatory pathway. Science 299, 233–6.
Karetsou, Z., Sandaltzopoulos, R., Frangou-Lazaridis, M., Lai, C.Y., Tsolas, O., Becker, P.B. & Papamarcaki, T. (1998). Prothymosin alpha modulates the interaction of histone H1 with chromatin. Nucleic Acids Res. 26, 3111–8.
Karetsou, Z., Kretsovali, A., Murphy, C., Tsolas, O. & Papamarcaki, T. (2002). Prothymosin alpha interacts with the CREB-binding protein and potentiates transcription. EMBO Rep. 3, 361–6.
Karetsou, Z., Martic, G., Tavoulari, S., Christoforidis, S., Wilm, M., Gruss, C. & Papamarcaki, T. (2004). Prothymosin alpha associates with the oncoprotein SET and is involved in chromatin decondensation. FEBS Lett. 577, 496500.
Leal, M.C., Cardoso, E.R., Nóbrega, R.H., Batlouni, S.R., Bogerd, J., França, L.R. & Schulz, R.W. (2009). Histological and stereological evaluation of zebrafish (Danio rerio) spermatogenesis with an emphasis on spermatogonial generations. Biol. Reprod. 81, 177–87.
Malicet, C., Giroux, V., Vasseur, S., Dagorn, J.C., Neira, J.L. & Iovanna, J.L. (2006). Regulation of apoptosis by the p8/prothymosin alpha complex. Proc. Natl. Acad. Sci. USA 103, 2671–6.
Martini, P.G. & Katzenellenbogen, B.S. (2003). Modulation of estrogen receptor activity by selective coregulators. J. Steroid. Biochem. Mol. Biol. 85, 117–22.
Martini, P.G., Delage-Mourroux, R., Kraichely, D.M. & Katzenellenbogen, B.S. (2000). Prothymosin alpha selectively enhances estrogen receptor transcriptional activity by interacting with a repressor of estrogen receptor activity. Mol. Cell. Biol. 20, 6224–32.
Moody, T.W., Leyton, J., Zia, F., Tuthill, C., Badamchian, M. & Goldstein, A.L. (2000). Thymosin alpha 1 is chemopreventive for lung adenoma formation in A/J mice. Cancer Lett. 155, 121–7.
Mosoian, A. (2011). Intracellular and extracellular cytokine-like functions of prothymosin α: implications for the development of immunotherapies. Future Med. Chem. 3, 1199–208.
Mosoian, A., Teixeira, A., Burns, C.S., Khitrov, G., Zhang, W., Gusella, L., Klotman, P. & Klotman, M. (2007). Influence of prothymosin-alpha on HIV-1 target cells. Ann. N.Y. Acad. Sci. 1112, 269–85.
Pan, L.X., Haritos, A.A., Wideman, J., Komiyama, T., Chang, M., Stein, S., Salvin, S.B. & Horecker, B.L. (1986). Human prothymosin alpha: amino acid sequence and immunologic properties. Arch. Biochem. Biophys. 250, 197201.
Papamarcaki, T. & Tsolas, O. (1994). Prothymosin alpha binds to histone H1 in vitro . FEBS Lett. 345, 71–5.
Parenti, L.R. & Grier, H.J. 2004. Evolution and phylogeny of gonad morphology in bony fishes. Integr. Comp. Biol. 44, 333–48.
Piñeiro, A., Cordero, O.J. & Nogueira, M. (2000). Fifteen years of prothymosin alpha: contradictory past and new horizons. Peptides 21, 1433–46.
Prisco, M., Donizetti, A., Aniello, F., Locascio, A., Del Giudice, G., Agnese, M., Angelini, F. & Andreuccetti, P. (2009). Expression of prothymosin alpha during the spermatogenesis of the spotted ray Torpedo marmorata . Gen. Comp. Endocrinol. 164, 70–6.
Pudney, J. (1996). Comparative cytology of the Leydig cell. In The Leydig Cell (eds Payne, A.M., Hardy, M.P. & Russell, L.D.), pp. 611–57. Vienna: Cache River.
Romani, L., Bistoni, F., Gaziano, R., Bozza, S., Montagnoli, C., Perruccio, K., Pitzurra, L., Bellocchio, S., Velardi, A., Rasi, G., Di Francesco, P. & Garaci, E. (2004). Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through Toll-like receptor signaling. Blood 103, 4232–9.
Rosón, E., Gallego, R., García-Caballero, T., Heimer, E.P., Felix, A.M. & Domínguez, F. (1990). Prothymosin alpha expression is associated to cell division in rat testis. Histochemistry 94, 597–9.
Rupik, W., Huszno, J. & Klag, J. (2011). Cellular organisation of the mature testes and stages of spermiogenesis in Danio rerio (Cyprinidae; Teleostei)—structural and ultrastructural studies. Micron 42, 833–9.
Sanger, F. & Coulson, A.R. (1975). A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J. Mol. Biol. 94, 441–8.
Schulz, R.W., de França, L.R., Lareyre, J.J., Le Gac, F., Chiarini-Garcia, H., Nobrega, R.H. & Miura, T. (2010). Spermatogenesis in fish. Comp. Endocrinol. 165, 390411.
Skopeliti, M., Voutsas, I.F., Klimentzou, P., Tsiatas, M.L., Beck, A., Bamias, A., Morak,i, M., Livaniou, E., Neagu, M., Voelter, W. & Tsitsilonis, O.E. (2006). The immunologically active site of prothymosin alpha is located at the carboxy-terminus of the polypeptide. Evaluation of its in vitro effects in cancer patients. Cancer Immunol. Immunother. 55, 1247–57.
Sprenger, H., Konrad, L., Rischowsky, E. & Gemsa, D. (1995). RNA extraction from gastrointestinaltract and pancreas by a modified Chomczynski and Sacchi method. Biotechniques 19, 340–3.
Tsitsiloni, O.E., Stiakakis, J., Koutselinis, A., Gogas, J., Markopoulos, C., Yialouris, P., Bekris, S., Panoussopoulos, D., Kiortsis, V. & Voelter, W. (1993). Expression of alpha-thymosins in human tissues in normal and abnormal growth. Proc. Natl. Acad. Sci. USA 90, 9504–7.
Ueda, H. (2009). Prothymosin alpha and cell death mode switch, a novel target for the prevention of cerebral ischemia-induced damage. Pharmacol. Ther. 123, 32333.
Ueda, H., Matsunaga, H. & Halder, S.K. (2012). Prothymosin α plays multifunctional cell robustness roles in genomic, epigenetic, and nongenomic mechanisms. Ann. N.Y. Acad. Sci. 1269, 3443.
Voutsas, I.F., Baxevanis, C.N., Gritzapis, A.D., Missitzis, I., Stathopoulos, G.P., Archodakis, G., Banis, C., Voelter, W. & Papamichail, M. (2000). Synergy between interleukin-2 and prothymosin alpha for the increased generation of cytotoxic T lymphocytes against autologous human carcinomas. Cancer Immunol. Immunother. 49, 449–58.
Wang, M. & Pan, J.Y. (2007). Prothymosin alpha and tumor: current status and perspective. Chin. J. Cancer 26, 333–6.
Wu, C.G., Habib, N.A., Mitry, R.R., Reitsma, P.H., van Deventer, S.J. & Chamuleau, R.A. (1997). Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma. Br. J. Cancer 76, 1199–204.
Wu, S.F., Zhang, H. & Cairns, B.R. (2011). Genes for embryo development are packaged in blocks of multivalent chromatin in zebrafish sperm. Genome Res. 21, 578–89.
Zhang, M., Cui, F., Lu, S., Lu, H., Jiang, T., Chen, J., Zhang, X., Jin, Y., Peng, Z. & Tang, H. (2014). Increased expression of prothymosin-α, independently or combined with TP53, correlates with poor prognosis in colorectal cancer. Int. J. Clin. Exp. Pathol. 7, 4867–76.
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Zygote
  • ISSN: 0967-1994
  • EISSN: 1469-8730
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