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Endocytic pathway of alpha-fetoprotein in mouse bone marrow hematopoietic stem cells: Molecular characterization and role in biological activity modification

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Abstract

The endocytic pathway of alpha-fetoprotein (AFP) in three types of mouse bone marrow hematopoietic stem cells (HSCs) different by the degree of maturity is similar to the natural pathway: it is based on receptor-mediated tranasport through the membrane p60, p65, and p305 AFP receptors with a clathrin-dependent mechanism of receptosome organization, in the formation and generation of which the AP-2 complex, endofilin, and dynamin are involved. In the studied types of HSCs, nongradient AFP was recorded in the Golgi complex, where it appeared by merging with the formed receptosome, as well as in the cytoplasm, endoplasmatic reticulum, and mitochondria, presumably through consequent binding with cytoplasmic carrier proteins (p55, p52, p62, and p67 AFP receptors) and also to transorganelle transporter proteins (p145 and p182 AFP receptors). A study of the role of AFP endocytosis in the modification of the biological activity of the studied HSC types has shown that it directly regulates protein synthesis and metabolic activity, while its effect on other examined types of biological activity was mediated by ERK1/2.

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References

  1. Mizejewski, G.J., Biological roles of alpha-fetoprotein during pregnancy and perinatal development, Exp. Biol. Med., 2004, vol. 229, pp. 439–463.

    CAS  Google Scholar 

  2. Yin, Z.F. and Wang, C.H., Research advances on alpha-fetoprotein physiological function and clinical potential, Ai Zheng, 2003, vol. 22, pp. 108–121.

    CAS  PubMed  Google Scholar 

  3. Mizejewski, G.J., Apha-fetoprotein as a biologic response modifier: relevance to domain and subdomain structure, Proc. Soc. Exp. Biol. Med, 1997, vol. 255, pp. 333–362.

    Article  Google Scholar 

  4. Trojan, J. and Uriel, J., Immunocytochemical localization of alpha-fetoprotein (AFP) and serum albumin (ALB) in ecto-, meso- and endodermal tissue derivatives of the developing rat, Oncodev. Biol. Med., 1982, vol. 3, pp. 13–22.

    CAS  PubMed  Google Scholar 

  5. Bogdanov, A.Yu., Suvorova, M.A., Kudrina, N.O., et al., The study of endocytosis of alpha-fetoprotein in hematopoietic bone marrow stem cells in vitro, Gigiena Epidemiol. Immunobiol., 2010, no. 3, pp. 130–135.

    Google Scholar 

  6. Torres, J.M., Geuskens, M., and Uriel, J., Activated human T lymphocytes express albumin binding proteins which cross-react with alpha-fetoprotein, Eur. J. Cell Biol., 1992, vol. 57, pp. 222–228.

    CAS  PubMed  Google Scholar 

  7. Geuskens, M., Torres, J.M., Esteban, C., and Uriel, J., Morphological characterization of the pathway of endocytosis and intracellular processing of transferring and alpha-fetoprotein in human T lymphocytes stimulated with phytohemagglutinin (PHA), Eur. J. Cell Biol., 1989, vol. 50, pp. 418–427.

    CAS  PubMed  Google Scholar 

  8. Laderoute, M.P., The characterization of a novel, widespread PHA-reactive tumor associated antigen: The alpha-fetoprotein receptor/binding protein, PhD Thesis, Alberta, 1991.

    Google Scholar 

  9. Mizejewski, G.J., Alpha-fetoprotein binding proteins: implications for transmembrane passage and sub-cellular localization, Life Sci., 1995, vol. 56, pp. 1–9.

    Article  CAS  PubMed  Google Scholar 

  10. Mizejewski, G.J., Review of the putative cell-surface receptors for alpha-fetoprotein: identification of a candidate receptor protein family, Tumor Biol., 2011, vol. 32, pp. 241–258.

    Article  CAS  Google Scholar 

  11. Mizejewski, G.J., Alpha-fetoprotein signal sequences: a proposed mechanism for subcellular localization and organelle targeting, J. Theor. Biol., 1995, vol. 176, pp. 103–113.

    Article  CAS  PubMed  Google Scholar 

  12. Laborda, J., Naval, J., Calvo, M., et al., Alpha-fetoprotein and albumin uptake by mouse tissues during development, J. Biol. Neonate, 1991, vol. 56, pp. 332–341.

    Article  Google Scholar 

  13. Aussel, C., Laliberti, F., and Masseyeff, R., Alpha-fetoprotein favours accumulation of estrone but not arachidonic acid into the fetal and new-born rat brain, Life Sci., 1985, vol. 36, pp. 479–484.

    Article  CAS  PubMed  Google Scholar 

  14. Mizejewski, G.J., Keenan, J.F., and Setty, R.P., Separation of the estrogen-activated growth regulatory forms of alpha-fetoprotein in mouse amniotic fluid, Biol. Red., 1990, vol. 42, pp. 887–898.

    Article  CAS  Google Scholar 

  15. Jacobson, H.I., Marotta, D., Mizijewski, G.J., et al., Estradiol-induced changes in spectral and biologic properties of alpha-fetoprotein, Proc. Int. Soc. Oncodev. Biol. Med., 1989, vol. 11, pp. 17–27.

    Google Scholar 

  16. Mizejeski, G.J., An apparent dimerization motif in the third domain of alpha-fetoprotein: molecular mimicry of the steroid/thyroid nuclear receptor superfamily, BioEssyas, 1993, vol. 15, pp. 427–432.

    Article  Google Scholar 

  17. Dauphinee, M.J. and Mizejewski, G.J., Human alphafetoprotein contains potential heterodimerization motifs capable of interaction with nuclear receptors and transcription/growth factors, Med. Hypotheses, 2002, vol. 58, pp. 453–461.

    Article  CAS  PubMed  Google Scholar 

  18. Bogdanov, A.Yu., Molecular mechanisms of activation of natural suppressor cells with alpha-fetoprotein, Extended Abstract of Cand. Sci. (Biol.) Dissertation, Almaty, 2005.

    Google Scholar 

  19. Bogdanova, T.M., Dubeshko, S.Y., Fomychova, E.V., et al., Alpha-fetoprotein effects on functional and morphological profile of the mice bone marrow hematopoietic stem cells ex vivo, Med. Vestn. Erebuni, 2010, no. 4, pp. 147–165.

    Google Scholar 

  20. Bogdanova, T.M., Dubeshko, S.Y., Fomychova, E.V., et al., Alpha-fetoprotein effects on functional and morphological profile of the mice bone marrow hematopoietic stem cells ex vivo, Med. Vestn. Erebuni, 2010, no. 4, pp. 147–165.

    Google Scholar 

  21. Bogdanova, T.M., Bogdanov, A.Yu., and Belyaev, N.N., Analysis of secondary messengers in the functional activity of hematopoietic stem cells during their induction with alpha-fetoprotein, Biotekhnol. Teor. Prakt., 2008, no. 1, pp. 70–81.

    Google Scholar 

  22. Bogdanov, A.Yu., Bogdanova, T.M., and Aitkhozhina, N.A., The role of cAMP-and ERK1/2-dependent cascades in the alpha-fetoprotein-induced functional change in the functional activity of bone marrow hematopoietic stem cells in vitro, Izv. Akad. Nauk Resp. Kaz., Ser. Biol., 2010, no. 3, pp. 30–36.

    Google Scholar 

  23. Bogdanov, A.Yu., Savvulidi, F.G., Tleulieva, R.T., and Belyaev, N.N., Alpha-fetoprotein as an inducer of bone marrow natural suppressor (NS) cells. 1. Isopycnal fraction of NS cells and their suppressor effects, Biotekhnol. Teor. Prakt., 2004, no. 3, pp. 83–89.

    Google Scholar 

  24. Sufiura, K., Ikehara, S., and Inaba, M., Enrichment of murine bone marrow natural suppressor activity in the fraction of hematopoietic progenitors with interleukin-3 receptor-associated antigen, Exp. Hematol., 1992, vol. 20, pp. 256–263.

    Google Scholar 

  25. Zakir’yanova, G.K. and Belyaev, N.N., Isopycnic separation of bone marrow cells, in Metody molekulyarnoi biologii, biokhimii, immunokhimii, biotekhnologii (Methods of Molecular Biology, Biochemistry, Immunochemistry, and Biotechnology), Almaty: Gridan, 1999, pp. 142–145.

    Google Scholar 

  26. Rosenberg, I.M., Protein Analysis and Purification, Boston: Birkhauser, 1996.

    Book  Google Scholar 

  27. Freshney, R.I., Culture of Animal Cells, New York: Wiley-Liss Inc., 2000.

    Google Scholar 

  28. Segerson, E.C. and Beetham, P.K., Suppressor activity of bone marrow cells and localization of fluorescent-labeled bone marrow cells within ovine and endometrial tissue, J. Anim. Sci., 2000, vol. 78, pp. 709–717.

    CAS  PubMed  Google Scholar 

  29. Rybakova, T.M., Nizkorodova, A.S., Zhigailov, A.V., et al., Membrane alpha-fetoprotein binding proteins of hematopoietic stem cells: structural, physical-chemical and biochemical properties, in VII Eur. Symp. of Protein Society (May 12–16, 2007, Sweden): Abstracts-Book, Stockholm: Uppsala Univ., 2007, p. 214.

    Google Scholar 

  30. Rybakova, T.M., Nizkorodova, A.S., Zhigailov, A.V., et al., Cytosol alpha-fetoprotein binding proteins of hematopoietic stem cells: structural, physical-chemical, biochemical and functional properties, in VII Eur. Symp. of Protein Society (May 12–16, 2007, Sweden): Abstracts-Book, Stockholm: Uppsala Univ., 2007, p. 149.

    Google Scholar 

  31. Alberts, B., Hohnson, A., Lewis, J., et al., Molecular Biology of the Cell, New York: Garland Publ., 2004, pp. 615–657.

    Google Scholar 

  32. Marsh, M., Endocytosis, London: Oxford Univ. Press, 2001.

    Google Scholar 

  33. Rybakova, T.M., Nizkorodova, A.S., Zhigailov, A.V., et al., Functional properties and attribute of hematopoietic stem cells membrane alpha-fetoprotein binding proteins, in Eur. Symp. of Protein Society (May 12–16, 2007, Stockholm, Sweden): Abstracts-Book, Stockholm: Uppsala Univ., 2007, p. 92.

    Google Scholar 

  34. Rappoport, J.Z., Focusing on clathrin-mediated endocytosis, Biochem. J., 2008, vol. 412, pp. 415–423.

    Article  CAS  PubMed  Google Scholar 

  35. Ellis, R.J., Molecular chaperones: assisting assembly in addition to folding, Trends Biochem. Sci., 2006, vol. 31, pp. 395–401.

    Article  CAS  PubMed  Google Scholar 

  36. Ellis, R.J., Protein misassembly: macromolecular crowding and molecular chaperones, Adv. Exp. Med. Biol., 2007, vol. 594, pp. 1–13.

    Article  PubMed  Google Scholar 

  37. McPherson, P.S., Kay, B.K., and Hussian, N.K., Signaling on the endocytic pathway, Traffic, 2004, vol. 2, pp. 375–384.

    Article  Google Scholar 

  38. Di Fiore, P.P. and Gill, G.N., Endocytosis and mitogenic signaling, Curr. Opin. Cell. Biol., 1999, vol. 11, pp. 483–488.

    Article  PubMed  Google Scholar 

Download references

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Correspondence to A. Yu. Bogdanov.

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Original Russian Text © A.Yu. Bogdanov, T.M. Bogdanova, A.I. Ilin, 2014, published in Tsitologiya i Genetika, 2014, Vol. 48, No. 1, pp. 25–40.

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Bogdanov, A.Y., Bogdanova, T.M. & Ilin, A.I. Endocytic pathway of alpha-fetoprotein in mouse bone marrow hematopoietic stem cells: Molecular characterization and role in biological activity modification. Cytol. Genet. 48, 21–32 (2014). https://doi.org/10.3103/S0095452714010034

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  • DOI: https://doi.org/10.3103/S0095452714010034

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