Abstract
ABCR is an ABC transporter that is found exclusively in vertebrate photoreceptor outer segments. Mutations in the human ABCR gene are responsible for autosomal recessive Stargardt disease, the most common cause of early onset macular degeneration. In this paper we review our recent work with purified and reconstituted ABCR derived from bovine retina and from cultured cells expressing wild type or site-directed mutants of human ABCR. These experiments implicate all-trans-retinal (or Schiff base adducts between all-trans-retinal and phosphatidylethanolamine) as the transport substrate, and they reveal asymmetric roles for the two nucleotide binding domains in the transport reaction. A model for the retinal transport reaction is presented which accounts for these experimental observations.
Similar content being viewed by others
REFERENCES
Ahn, J., Wong, J. T., and Molday, R. S. (2000). J. Biol. Chem. 275, 20399–20405.
Allikmets, R., Singh, N., Sun, H., Shroyer, N. F., Hutchinson, A., Chidambaram, A., Gerrard, B., Baird, L., Stauffer, D., Peiffer, A., Rattner, A., Smallwood, P., Li, Y., Anderson, K. L., Lewis, R. A., Nathans, J., Leppert, M., Dean, M., and Lupski, J. R. (1997a). Nat. Genet. 15, 236–246.
Allikmets, R., Shroyer, N. F., Singh, N., Seddon, J. M., Lewis, R. A., Bernstein, P., Peiffer, A., Zabriskie, N., Li, Y., Hutchinson, A., Dean, M., Lupski, J. R., and Leppert, M. (1997b). Science 277, 1805–1807.
Allikmets, R., and the International ABCR Screening Consortium. (2000). Am. J. Hum. Genet. 67, 487–491.
Alpern, M. (1971). J. Physiol. 217, 447–471.
Alpern, M., Rushton, W. A. H., and Torii, S. (1970). J. Physiol. 207, 449–461.
Ambudkar, S. V., Lelong, I. H., Zhang, J. P., Carderelli, C. O., Gottesman, M. M., and Pastan, I. (1992). Proc. Natl. Acad. Sci.U.S.A. 89, 8472–8476.
Blacharski, P. A. (1988). In Retinal Dystrophies and Degenerations (Newsome, D. A., ed.), Raven, New York, pp. 135–159.
Buczylko, J. B., Saari, J. C., Crouch, R., and Palczewski, K. (1996). J. Biol. Chem. 271, 20621–20630.
Cohen, G. B., Oprian, D. D., and Robinson, P. R. (1992). Biochemistry 31, 12592–12601.
Cremers, F. P. M., van de Pol, D. J. R., van Driel, M., den Hollander, A. I., van Haren, F. J. J., Knoers, N. V. A. M., Tijmes, N., Bergen, A. A. B., Rohrschneider, K., Blankenagel, A., Pinckers, A. J. L. G., Deutman, A. F., and Hoyng, C. B. (1998). Hum. Mol. Genet. 7, 355–362.
Delori, F. C., Dorey, C. K., Staurenghi,. G., Arend, O., Goger, D. G., and Weiter, J. J. (1995a). Invest. Ophthalmol. Vis. Sci. 36, 718–729.
Delori, F. C., Staurenghi, G., Arend, O., Dorey, C. K., Goger, D. G., and Weiter, J. J. (1995b). Invest. Ophthalmol. Vis. Sci. 36, 2327–2331.
Eagle, R. C., Lucier, A. C., Bernardino, V. B., and Yanoff, M. (1980). Opthalmology 87, 1189–1200.
Eldred, G. E., and Lasky, M. R. (1993). Nature 361, 724–726.
Fain, G. L., Matthews, H. R., and Cornwall, M. C. (1996). Trends Neurosci. 19, 502–507.
Fishman, G. A., Farbman, J. S., and Alexander, K. R. (1991). Ophthalmology 98, 957–962.
Hung, L.-W., Wang, I. X., Nikaido, K., Liu, P.-Q., Ferro-Luzzi Ames, G., and Kim, S.-H. (1998). Nature 396, 703–707.
Illing, M., Molday, L. L., and Molday, R. S. (1997). J. Biol. Chem. 272, 10303–10310.
Jager, S., Palczewski, K., and Hofmann, K. P. (1996). Biochemistry 35, 2901–2908.
Klein, B. A., and Krill, A. E. (1967). Am. J. Opthalmol. 64, 3–23.
Lamb, T. D. (1980). Nature 87, 349–351.
Lehninger, A. (1975). Biochemistry, Worth Publishers, New York, pp. 183–216.
Lewis, R. A., Shroyer, N. F., Singh, N., Allikmets, R., Hutchinson, A., Li, Y., Lupski, J. R., Leppert, M., and Dean, M. (1999). Am. J. Hum. Genet. 64, 422–434.
Lion, F., Rotmans, J. P., Daemen, F. J. M., and Bonting, S. L. (1975). Biochem. Biophys. Acta 384, 283–292.
Martinez-Mir, A., Paloma, E., Allikmets, R., Ayoso, C., del Rio, T., Dean, M., Gonzalez-Duarte, R., and Balcells, S. (1998). Nat. Genet. 18, 11–12.
Mata, N. L., Weng, J., and Travis, G. H. (2000). Proc. Natl. Acad. Sci. U.S.A. 97, 7154–7159.
Maugeri, A., van Driel, M. A., van de Pol, D. J. R., Klevering, B. J., van Haren, F. J. J., Tijmes, N., Bergen, A. A. B., Rohrschneider, K., Blankenagel, A., Pinckers, A. J. L. G., Dahl, N., Brunner, H. G., Deutman, A. F., Hoyng, C. B., and Cremers, F. P. M. (1999). Am. J. Hum. Genet. 64, 1024–1035.
Molday L. L., Rabin A. R., and Molday R. S. (2000). Nat. Genet. 25, 257–258.
Nasonkin, I., Illing, M., Koehler, M. R., Schmid, M., Molday, R. S., and Weber, B. H. F. (1998). Hum. Genet. 102, 21–26.
Palczewski, K., Jager, S., Buczylko, J., Crouch, R. K., Bredberg, D. L., Hofmann, K. P., Asson-Batres, M. A., and Saari, J. C. (1994). Biochemistry 33, 13741–13750.
Parish, C. A., Hashimoto, M., Nakanishi, K., Dillon, J., and Sparrow, J. (1998). Proc. Natl. Acad. Sci. U.S.A. 95, 14609–14613.
Rattner, A., Smallwood, P. M., and Nathans, J. (2000). J. Biol. Chem. 275, 11034–11043.
Rozet J.-M., Gerber, S., Souied, E., Perrault, I., Chatelin, S., Ghazi, I., Leowski, C., Dufier, J.-L., Munnich, A., and Kaplan, J. (1998). Eur. J. Hum. Genet. 6, 291–295.
Rozet, J.-M., Gerber, S., Ghazi, I., Perrault, I., Ducroq, D., Souied, E., Cabot, A., Dufier, J.-L., Munnich, A., and Kaplan, J. (1999). J. Med. Genet. 36, 447–451.
Saari, J. C., Garwin, G. G., Van Hooser, J. P., and Palczewski, K. (1998). Vision Res. 38, 1325–1333.
Sakai, N., Decataur, J., Nakanishi, K., and Eldred, G. E. (1996). J. Am. Chem. Soc. 118, 1559–1660.
Sarkadi, B., Price, E. M., Boucher, R. C., Germann, U. A., and Scarborough, G. A. (1992). J. Biol. Chem. 267, 4854–4858.
Segel, I. H. (1976). Biochemical Calculations, Wiley, New York, pp. 246–266.
Shapiro, A., and Ling, V. (1994). J. Biol. Chem. 269, 3745–3754.
Sparrow, J. R., Nakanishi, K., and Parish, C. A. (2000). Invest. Ophthalmol. Vis. Sci. 41, 1981–1989.
Steinmetz, R. L., Garner, A., Maguirre, J. I., and Bird, A. C. (1991). Ophthalmology 98, 953–956.
Stone, E. M., Webster, A. R., Vandenburgh, K., Streb, L. M., Hockey, R. R., Lotery, A. J., and Sheffield, V. C., (1998). Nat. Genet. 20, 328–329.
Sun, H., and Nathans, J. (1997). Nat. Genet. 17, 15–16.
Sun, H., Molday, R. S., and Nathans, J. (1999). J. Biol. Chem. 274, 8269–8281.
Sun, H., Smallwood, P. M., and Nathans, J. (2000). Nat. Genet. 26, 242–246.
Surya, A., Foster, K. W., and Knox, B. E. (1995). J. Biol. Chem. 270, 5024–5031.
Urbatsch, I. L., Al-Shawi, M. K., and Senior, A. E. (1994). Biochemistry 33, 7069–7076.
Weng, J., Mata, N. L., Azarian, S. M., Tzekov, R. D., Birch, D. G., and Travis, G. H. (1999). Cell 98, 13–23.
Zimmerman, W. H., Yost, M. T., and Daemen, F. J. M. (1974). Nature 250, 66–67.
Rights and permissions
About this article
Cite this article
Sun, H., Nathans, J. Mechanistic Studies of ABCR, the ABC Transporter in Photoreceptor Outer Segments Responsible for Autosomal Recessive Stargardt Disease. J Bioenerg Biomembr 33, 523–530 (2001). https://doi.org/10.1023/A:1012883306823
Issue Date:
DOI: https://doi.org/10.1023/A:1012883306823