Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-10T08:47:51.923Z Has data issue: false hasContentIssue false
  • English
  • Français

Prothymosin alpha expression and localization during the spermatogenesis of Danio rerio

Published online by Cambridge University Press:  09 October 2015

Paolo Pariante ,
Raffaele Dotolo ,
Massimo Venditti ,
Diana Ferrara ,
Aldo Donizetti ,
Francesco Aniello  and
Sergio Minucci
Paolo Pariante*
Affiliation:
Dipartimento di Medicina Sperimentale, Seconda Università di Napoli. 80138, Napoli, Italy.
Raffaele Dotolo
Affiliation:
Dipartimento di Medicina Sperimentale, Sez. Fisiologia Umana e Funzioni Biologiche Integrate ‘F. Bottazzi’ Seconda Università di Napoli. 80138, Napoli, Italy.
Massimo Venditti
Affiliation:
Dipartimento di Medicina Sperimentale, Sez. Fisiologia Umana e Funzioni Biologiche Integrate ‘F. Bottazzi’ Seconda Università di Napoli. 80138, Napoli, Italy.
Diana Ferrara
Affiliation:
Dipartimento di Medicina Sperimentale, Sez. Fisiologia Umana e Funzioni Biologiche Integrate ‘F. Bottazzi’ Seconda Università di Napoli. 80138, Napoli, Italy.
Aldo Donizetti
Affiliation:
Dipartimento di Biologia, Università di Napoli Federico II. 80126, Napoli, Italy.
Francesco Aniello
Affiliation:
Dipartimento di Biologia, Università di Napoli Federico II. 80126, Napoli, Italy.
Sergio Minucci*
Affiliation:
Dipartimento di Medicina Sperimentale, Seconda Università di Napoli. 80138, Napoli, Italy.
*
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
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
Get access Rights & Permissions [Opens in a new window]

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.

Keywords

Prothymosin alphaSpermatogenesisSpermatozoaTestisZebrafish
Type
Research Article
Information
Zygote , Volume 24 , Issue 4 , August 2016 , pp. 583 - 593
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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.Google Scholar
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.Google Scholar
Billard, R. (1990). Spermatogenesis in teleost fish. In Marshall's Physiology of Reproduction. Reproduction in Males, vol. 2 (ed. Lamming, G.E.), pp. 183–212. Edinburgh: Churchill Livingston.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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. .CrossRefGoogle ScholarPubMed
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, 1–10.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
Hannappel, E. & Huff, T. (2003). The thymosins. Prothymosin alpha, parathymosin, and beta-thymosins: structure and function. Vitam. Horm. 66, 257–96.Google Scholar
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.Google Scholar
Haritos, A.A., Tsolas, O. & Horecker, B.L. (1984b). Distribution of prothymosin alpha in rat tissues. Proc. Natl. Acad. Sci. USA 81, 1391–3.Google Scholar
Hirai, A. (1988). Fine structure of the micropyles of pelagic eggs of some marine fishes. Jap. J. Ichthyol. 35, 351–7.Google Scholar
Huszno, J. & Klag, J. (2012). The reproductive cycle in the male gonads of Danio rerio (Teleostei, Cyprinidae). Stereological analysis. Micron 43, 666–72.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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, 496–500.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Martini, P.G. & Katzenellenbogen, B.S. (2003). Modulation of estrogen receptor activity by selective coregulators. J. Steroid. Biochem. Mol. Biol. 85, 117–22.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
Mosoian, A. (2011). Intracellular and extracellular cytokine-like functions of prothymosin α: implications for the development of immunotherapies. Future Med. Chem. 3, 1199–208.Google Scholar
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.Google Scholar
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, 197–201.CrossRefGoogle ScholarPubMed
Papamarcaki, T. & Tsolas, O. (1994). Prothymosin alpha binds to histone H1 in vitro . FEBS Lett. 345, 71–5.Google Scholar
Parenti, L.R. & Grier, H.J. 2004. Evolution and phylogeny of gonad morphology in bony fishes. Integr. Comp. Biol. 44, 333–48.Google Scholar
Piñeiro, A., Cordero, O.J. & Nogueira, M. (2000). Fifteen years of prothymosin alpha: contradictory past and new horizons. Peptides 21, 1433–46.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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, 390–411.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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, 34–43.Google Scholar
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.Google Scholar
Wang, M. & Pan, J.Y. (2007). Prothymosin alpha and tumor: current status and perspective. Chin. J. Cancer 26, 333–6.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar