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Retinoids pp 341-361 | Cite as

Techniques to Study Specific Cell-Surface Receptor-Mediated Cellular Vitamin A Uptake

  • Riki Kawaguchi
  • Hui Sun
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 652)

Abstract

STRA6 is a multitransmembrane domain protein that was recently identified as the cell-surface receptor for plasma retinol-binding protein (RBP), the vitamin A carrier protein in the blood. STRA6 binds to RBP with high affinity and mediates cellular uptake of vitamin A from RBP. It is not homologous to any known receptors, transporters, and channels, and it represents a new class of membrane transport protein. Consistent with the diverse physiological functions of vitamin A, STRA6 is widely expressed in diverse adult organs and throughout embryonic development. Mutations in human STRA6 that abolish its vitamin A uptake activity cause severe pathological phenotypes in many human organs including the eye, brain, lung, and heart. This chapter describes functional assays for STRA6 in live cells and on cellular membranes. These assays can be employed to study the mechanism of this new membrane transport mechanism and its roles in the physiology and pathology of many organs.

Key words

STRA6 retinol-binding protein receptor retinol retinyl ester vitamin A retinoid vitamin A uptake HPLC 

References

  1. 1.
    Blomhoff, R. (1994) Overview of vitamin A metabolism and function. In: Blomhoff, R. (ed.), Vitamin A in Health and Disease, Marcel Dekker, Inc., New York, Basel, Hong Kong, pp. 1–35.Google Scholar
  2. 2.
    Ross, A.C., Gardner, E.M. (1994) The function of vitamin A in cellular growth and differentiation, and its roles during pregnancy and lactation. Adv. Exp. Med. Biol. 352, 187–200.PubMedGoogle Scholar
  3. 3.
    Napoli, J.L. (1996) Biochemical pathways of retinoid transport, metabolism, and signal transduction. Clin. Immunol. Immunopathol. 80, S52–S62.PubMedCrossRefGoogle Scholar
  4. 4.
    Evans, R.M. (1994) The molecular basis of signaling by vitamin A and its metabolites. Harvey Lect. 90, 105–117.PubMedGoogle Scholar
  5. 5.
    Chambon, P. (1996) A decade of molecular biology of retinoic acid receptors. FASEB J. 10, 940–954.PubMedGoogle Scholar
  6. 6.
    Maden, M. (1994) Role of retinoids in embryonic development. In: Blomhoff, R. (ed.), Vitamin A in Health and Disease, Marcel Dekker, Inc., New York, Basel, Hong Kong.Google Scholar
  7. 7.
    Duester, G. (2008) Retinoic acid synthesis and signaling during early organogenesis. Cell 134, 921–931.PubMedCrossRefGoogle Scholar
  8. 8.
    Drager, U.C. (2006) Retinoic acid signaling in the functioning brain. Sci STKE 2006, pe10.CrossRefGoogle Scholar
  9. 9.
    Blomhoff, H.K., Smeland, E.B. (1994) Role of retinoids in normal hematopoiesis and the immune system. In: Blomhoff, R. (ed.), Vitamin A in Health and Disease, Marcel Dekker, Inc., pp. 451–484Google Scholar
  10. 10.
    Stephensen, C.B. (2001) Vitamin A, infection, and immune function. Annu. Rev. Nutr. 21, 167–192.PubMedCrossRefGoogle Scholar
  11. 11.
    Chung, S.S., Wolgemuth, D.J. (2004) Role of retinoid signaling in the regulation of spermatogenesis. Cytogenet. Genome Res. 105, 189–202.PubMedCrossRefGoogle Scholar
  12. 12.
    Wolbach, S.R., Howe, P.R. (1925) Tissue change following deprivation of fat-soluble A vitamin. J. Exp. Med. 42, 753–777.PubMedCrossRefGoogle Scholar
  13. 13.
    Biesalski, H.K. (2003) The significance of vitamin A for the development and function of the lung. Forum Nutr. 56, 37–40.PubMedGoogle Scholar
  14. 14.
    Vahlquist, A. (1994) Role of retinoids in normal and diseased skin. In: Blomhoff, R. (ed.), Vitamin A in Health and Disease, Marcel Dekker, Inc., New York, Basel, Hong Kong, pp 365–424.Google Scholar
  15. 15.
    Chen, N., Onisko, B., Napoli, J.L. (2008) The nuclear transcription factor RARalpha associates with neuronal RNA granules and suppresses translation. J. Biol. Chem. 283, 20841–20847.PubMedCrossRefGoogle Scholar
  16. 16.
    Aoto, J., Nam, C.I., Poon, M.M., Ting, P., Chen, L. (2008) Synaptic signaling by all-trans retinoic acid in homeostatic synaptic plasticity. Neuron 60, 308–320.PubMedCrossRefGoogle Scholar
  17. 17.
    Travis, G.H., Golczak, M., Moise, A.R., Palczewski, K. (2007) Diseases caused by defects in the visual cycle: Retinoids as potential therapeutic agents. Annu. Rev. Pharmacol. Toxicol. 47, 469–512.PubMedCrossRefGoogle Scholar
  18. 18.
    Ziouzenkova, O., Orasanu, G., Sharlach, M., Akiyama, T.E., Berger, J.P., Viereck, J., Hamilton, J.A., Tang, G., Dolnikowski, G.G., Vogel, S., Duester, G., Plutzky, J. (2007) Retinaldehyde represses adipogenesis and diet-induced obesity. Nat. Med. 13, 695–702.PubMedCrossRefGoogle Scholar
  19. 19.
    Buck, J., Myc, A., Garbe, A., Cathomas, G. (1991) Differences in the action and metabolism between retinol and retinoic acid in B lymphocytes. J. Cell Biol. 115, 851–859.PubMedCrossRefGoogle Scholar
  20. 20.
    Chen, Y., Derguini, F., Buck, J. (1997) Vitamin A in serum is a survival factor for fibroblasts. Proc. Natl. Acad. Sci. USA 94, 10205–10208.PubMedCrossRefGoogle Scholar
  21. 21.
    Baleato, R.M., Aitken, R.J., Roman, S.D. (2005) Vitamin A regulation of BMP4 expression in the male germ line. Dev. Biol. 286, 78–90.PubMedCrossRefGoogle Scholar
  22. 22.
    Chen, L., Khillan, J.S. (2008) Promotion of feeder-independent self-renewal of embryonic stem cells by retinol (vitamin A). Stem Cells 26, 1858–1864.PubMedCrossRefGoogle Scholar
  23. 23.
    Blomhoff, R., Green, M.H., Berg, T., Norum, K.R. (1990) Transport and storage of vitamin A. Science 250, 399–404.PubMedCrossRefGoogle Scholar
  24. 24.
    Newcomer, M.E., Ong, D.E. (2000) Plasma retinol binding protein: Structure and function of the prototypic lipocalin. Biochim. Biophys. Acta 1482, 57–64.PubMedCrossRefGoogle Scholar
  25. 25.
    Zanotti, G., Berni, R. (2004) Plasma retinol-binding protein: Structure and interactions with retinol, retinoids, and transthyretin. Vitam. Horm. 69, 271–295.PubMedCrossRefGoogle Scholar
  26. 26.
    Quadro, L., Hamberger, L., Gottesman, M.E., Wang, F., Colantuoni, V., Blaner, W.S., Mendelsohn, C.L. (2005) Pathways of vitamin A delivery to the embryo: Insights from a new tunable model of embryonic vitamin A deficiency. Endocrinology 146, 4479–4490.PubMedCrossRefGoogle Scholar
  27. 27.
    Bok, D., Heller, J. (1976) Transport of retinol from the blood to the retina: An autoradiographic study of the pigment epithelial cell surface receptor for plasma retinol-binding protein. Exp. Eye Res. 22, 395–402.PubMedCrossRefGoogle Scholar
  28. 28.
    Heller, J. (1975) Interactions of plasma retinol-binding protein with its receptor. Specific binding of bovine and human retinol-binding protein to pigment epithelium cells from bovine eyes. J. Biol. Chem. 250, 3613–3619.PubMedGoogle Scholar
  29. 29.
    Heller, J., Bok, D. (1976) Transport of retinol from the blood to the retina: Involvement of high molecular weight lipoproteins as intracellular carriers. Exp. Eye Res. 22, 403–410.PubMedCrossRefGoogle Scholar
  30. 30.
    Rask, L., Peterson, P.A. (1976) In vitro uptake of vitamin A from the retinol-binding plasma protein to mucosal epithelial cells from the monkey's small intestine. J. Biol. Chem. 251, 6360–6366.PubMedGoogle Scholar
  31. 31.
    Maraini, G., Gozzoli, F. (1975) Binding of retinol to isolated retinal pigment epithelium in the presence and absence of retinol-binding protein. Invest. Ophthalmol. 14, 785–787.PubMedGoogle Scholar
  32. 32.
    Chen, C.C., Heller, J. (1977) Uptake of retinol and retinoic acid from serum retinol-binding protein by retinal pigment epithelial cells. J. Biol. Chem. 252, 5216–5221.PubMedGoogle Scholar
  33. 33.
    Sivaprasadarao, A., Findlay, J.B. (1988) The interaction of retinol-binding protein with its plasma-membrane receptor. Biochem. J. 255, 561–569.PubMedGoogle Scholar
  34. 34.
    Smeland, S., Bjerknes, T., Malaba, L., Eskild, W., Norum, K.R., Blomhoff, R. (1995) Tissue distribution of the receptor for plasma retinol-binding protein. Biochem. J. 305(Pt 2), 419–424.PubMedGoogle Scholar
  35. 35.
    Sivaprasadarao, A., Boudjelal, M., Findlay, J.B. (1994) Solubilization and purification of the retinol-binding protein receptor from human placental membranes. Biochem. J. 302(Pt 1), 245–251.PubMedGoogle Scholar
  36. 36.
    MacDonald, P.N., Bok, D., Ong, D.E. (1990) Localization of cellular retinol-binding protein and retinol-binding protein in cells comprising the blood-brain barrier of rat and human. Proc. Natl. Acad. Sci. USA 87, 4265–4269.PubMedCrossRefGoogle Scholar
  37. 37.
    Shingleton, J.L., Skinner, M.K., Ong, D.E. (1989) Characteristics of retinol accumulation from serum retinol-binding protein by cultured Sertoli cells, Biochemistry 28, 9641–9647.PubMedCrossRefGoogle Scholar
  38. 38.
    Bishop, P.D., Griswold, M.D. (1987) Uptake and metabolism of retinol in cultured Sertoli cells: Evidence for a kinetic model. Biochemistry 26, 7511–7518.PubMedCrossRefGoogle Scholar
  39. 39.
    Bhat, M.K., Cama, H.R. (1979) Gonadal cell surface receptor for plasma retinol-binding protein. A method for its radioassay and studies on its level during spermatogenesis. Biochim. Biophys. Acta 587, 273–281.PubMedCrossRefGoogle Scholar
  40. 40.
    Davis, J.T., Ong, D.E. (1995) Retinol processing by the peritubular cell from rat testis. Biol. Reprod. 52, 356–364.PubMedCrossRefGoogle Scholar
  41. 41.
    Hagen, E., Myhre, A.M., Smeland, S., Halvorsen, B., Norum, K.R., Blomhoff, R. (1999) Uptake of vitamin A in macrophages from physiologic transport proteins: Role of retinol-binding protein and chylomicron remnants. J. Nutr. Biochem. 10, 345–352.PubMedCrossRefGoogle Scholar
  42. 42.
    Torma, H., Vahlquist, A. (1984) Vitamin A uptake by human skin in vitro. Arch. Dermatol. Res. 276, 390–395.PubMedCrossRefGoogle Scholar
  43. 43.
    Buck, J., Ritter, G., Dannecker, L., Katta, V., Cohen, S.L., Chait, B.T., Hammerling, U. (1990) Retinol is essential for growth of activated human B cells. J. Exp. Med. 171, 1613–1624.PubMedCrossRefGoogle Scholar
  44. 44.
    Kawaguchi, R., Yu, J., Honda, J., Hu, J., Whitelegge, J., Ping, P., Wiita, P., Bok, D., Sun, H. (2007) A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 315, 820–825.PubMedCrossRefGoogle Scholar
  45. 45.
    Bouillet, P., Sapin, V., Chazaud, C., Messaddeq, N., Decimo, D., Dolle, P., Chambon, P. (1997) Developmental expression pattern of Stra6, a retinoic acid-responsive gene encoding a new type of membrane protein. Mech. Dev. 63, 173–186.PubMedCrossRefGoogle Scholar
  46. 46.
    Szeto, W., Jiang, W., Tice, D.A., Rubinfeld, B., Hollingshead, P.G., Fong, S.E., Dugger, D.L., Pham, T., Yansura, D.G., Wong, T.A., Grimaldi, J.C., Corpuz, R.T., Singh, J.S., Frantz, G.D., Devaux, B., Crowley, C.W., Schwall, R.H., Eberhard, D.A., Rastelli, L., Polakis, P., Pennica, D. (2001) Overexpression of the retinoic acid-responsive gene Stra6 in human cancers and its synergistic induction by Wnt-1 and retinoic acid. Cancer Res. 61, 4197–4205.PubMedGoogle Scholar
  47. 47.
    Pasutto, F., Sticht, H., Hammersen, G., Gillessen-Kaesbach, G., Fitzpatrick, D.R., Nurnberg, G., Brasch, F., Schirmer-Zimmermann, H., Tolmie, J.L., Chitayat, D., Houge, G., Fernandez-Martinez, L., Keating, S., Mortier, G., Hennekam, R.C., von der Wense, A., Slavotinek, A., Meinecke, P., Bitoun, P., Becker, C., Nurnberg, P., Reis, A., Rauch, A. (2007) Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation. Am. J. Hum. Genet. 80, 550–560.PubMedCrossRefGoogle Scholar
  48. 48.
    Golzio, C., Martinovic-Bouriel, J., Thomas, S., Mougou-Zrelli, S., Grattagliano-Bessieres, B., Bonniere, M., Delahaye, S., Munnich, A., Encha-Razavi, F., Lyonnet, S., Vekemans, M., Attie-Bitach, T., Etchevers, H.C. (2007) Matthew-Wood syndrome is caused by truncating mutations in the retinol-binding protein receptor gene STRA6. Am. J. Hum. Genet. 80, 1179–1187.PubMedCrossRefGoogle Scholar
  49. 49.
    Kawaguchi, R., Yu, J., Wiita, P., Honda, J., Sun, H. (2008) An essential ligand-binding domain in the membrane receptor for retinol-binding protein revealed by large-scale mutagenesis and a human polymorphism. J. Biol. Chem. 283, 15160–15168.PubMedCrossRefGoogle Scholar
  50. 50.
    Kawaguchi, R., Yu, J., Wiita, P., Ter-Stepanian, M., Sun, H. (2008) Mapping the membrane topology and extracellular ligand binding domains of the retinol binding protein receptor. Biochemistry 47, 5387–5395.PubMedCrossRefGoogle Scholar
  51. 51.
    Flanagan, J.G., Cheng, H.J. (2000) Alkaline phosphatase fusion proteins for molecular characterization and cloning of receptors and their ligands. Methods Enzymol. 327, 198–210.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Riki Kawaguchi
    • 1
  • Hui Sun
    • 1
  1. 1.Department of Physiology, Jules Stein Eye Institute, and Brain Research Institute, David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA

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