Summary
Impressive arrays of highly structurally and functionally conserved proteins have dedicated roles in Cu ion transport and distribution. Many questions remain to be answered in the field of Cu ion homeostasis. Currently, it is unclear exactly what mechanisms are used by the plasma membrane Cu transport proteins to safely move Cu ions across biological membranes. Are these proteins functioning alone or in a large metal ion-transporting complex? Further, once Cu is imported, how do Cu chaperones obtain their Cu cargo for delivery to proteins and cellular compartments? These and related questions are of great importance in formulating a comprehensive understanding of the molecular basis for Cu ion transport and distribution in all cells.
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References
Amaravadi, R., Glerum, D.M., and Tzagoloff, A., 1997, Isolation of a cDNA encoding the human homolog of COX17, a yeast gene essential for mitochondrial copper recruitment, Hum. Genet. 99:329–333.
Askwith, C., Eide, D., Ho, A.V., Bernard, P.S., Li, L., Davis-Kaplan, S., Sipe, D.M., and Kaplan, J., 1994, The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake, Cell 76:403–410.
Bull, P.C. and Cox, D.W., 1994, Wilson disease and Menkes disease: new handles on heavy-metal transport, Trends in Genet. 10:246–252.
Casareno, R.L.B., Waggoner, D., and Gitlin, J.D., 1998, The copper chaperone CCS directly interacts with copper/zinc superoxide dismutase, J. Biol. Chem. 273:23625–23628.
Culotta, V.C., Klomp, L.W.J., Strain, J., Casareno, L.B., Krems, B., and Giltin, J.D., 1997, The Copper chaperone for superoxide dismutase, J. Biol. Chem. 272:23469–23472.
Dancis, A., Haile, D., Yuan, D.S., and Klausner, R.D., 1994a, The Saccharomyces cerevisiae copper transport protein (Ctrlp). Biochemical characterization, regulation by copper, and physiologic role in copper uptake, J. Biol. Chem. 269:25660–25667.
Dancis, A., Yuan, D.S., Haile, D., Askwith, C., Eide, D., Moehle, C., Kaplan, J., and Klausner, R.D., 1994b, Molecular characterization of a copper transport protein in S. cerevisiae: An unexpected role for copper in iron transport, Cell 76:393–402.
DiDonato, M. and Sarkar, B., 1997, Copper transport and its alterations in Menkes and Wilson diseases, Biochem. Biophy. Acta 1360:3–16.
Georgatsou, E. and Alexandraki, D., 1994, Two distinctly regulated genes are required for ferric reduction, the first step of iron uptake in Saccharomyces cerevisiae, Mol. Cell. Biol. 14:3065–3073.
Georgatsou, E., Mavrogiannis, L.A., Fragiadakis, G.S., and Alexandraki, D., 1997, The yeast Frelp/Fre2p cupric reductase facilitate copper uptake and are regulated by the copper-modulated Macl activator, J. Biol. Chem. 272, 13786–13792.
Glerum, D.M., Shtanko, A., and Tzagoloff, A., 1996, Characterization of COX17, a yeast gene involved in copper metabolism and assembly of cytochrome oxidase, J. Biol. Chem. 271:14504–14509.
Halliwell, B. and Gutteridge, J.M.C., 1984, Oxygen toxicity, oxygen radicals, transition metals and disease, Biochem. J. 219:1–14.
Hassett, R. and Kosman, D.J., 1995, Evidence of Cu(II) reduction as a component of copper uptake by Saccharomyces cerevisiae, J. Biol. Chem. 270:128–134.
Jensen, L.T. and Winge, D.R., 1998, Identification of a copper-induced intramolecular interaction in the transcription factor Macl from Saccharomyces cerevisiae, EMBO 17:5400–5408.
Klomp, L.W.J., Lin, S.-J., Yuan, D.S., Klausner, R.D., Culotta, V.C., and Gitlin, J.D., 1997, Idnetification and functional expression of HAH1, a novel human gene involved in copper homeostasis, J. Biol. Chem. 272:9221–9226.
Knight, S.A.B., Labbe, S., Kwon, L.F., Kosman, D.J., and Thiele, D.J., 1996, A widespread transposable element masks expression of a yeast copper transport gene, Genes & Dev. 10:1917–1929.
Labbe, S., Zhu, Z., and Thiele, D.J., 1997, Copper-specific transcriptional repression of yeast genes encoding critical components in the copper transcription pathway, J. Biol. Chem. 272:15951–15958.
Lin, S.-J. and Culotta, V.C., 1995, The ATX1 gene of Saccharomyces cerevisiae encodes a small metal homeostasis factor that protects cells against reactive oxygen toxicity, Proc. Natl. Acad. Sci. USA 92:3784–3788.
Lin, C.M. and Kosman, D.J., 1990, Copper uptake in wild type and copper metallothionein-deficient Saccharomyces cerevisiae. Kinetics and mechanism, J. Biol. Chem. 265:9194–9200.
Lin, S.-J., Pufahl, R.A., Dancis, A., O’Halloran, TV., and Culotta, V.C., 1997, A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking and iron transport, J. Biol. Chem. 272:9215–9220.
Linder, M.C., 1991, Biochemistry of copper, Plenum Press, New York.
Martins, L.J., Jensen, L.T, Simons, J.R., Keller, G.L., and Winge, D.R., 1998, Metalloregulation of FRE1 and FRE2 homologs in Saccharomyces cerevisiae, J. Biol. Chem. 273:23716–23721.
Pena, M.M.O., Koch, K.A., and Thiele, D.J., 1998, Dynamic regulation of copper uptake and detoxification genes in Saccharomyces cerevisiae, Mol. Cell Biol. 18:2514–2523.
Pufahl, R.A., Singer, C.P., Peariso, K.L., Lin, S.-J., Schmidt, P.J., Fahrni, C.J., Culotta, V.C., Penner-Hahn, J.E., and O’Halloran, T.V., 1997, Metal ion chaperone function of the soluble Cu(I) receptor Atx1, Science 278:853–856.
Stearman, R., Yuan, D.S., Yamaguchi-Iwai, Y., Klausner, R.D., and Dancis, A., 1996, A permease-oxidase complex involved in high-affinity iron uptake in yeast, Science 271:1552–1557.
Yamaguchi-Iwai, Y., Serpe, M., Haile, D., Yang, W., Kosman, D., Klausner, R.D., and Dancis, A., 1997, Homeostatic regulation of copper uptake in yeast via direct binding of MAC1 protein to upstream regulatory sequences of FRE1 and CTR1, J. Biol. Chem. 272:17711–17718.
Yuan, D.S., Stearman, R., Dancis, A., Dunn, T., Beeler, T., and Klausner, R.D., 1995, The Menkes/Wilson disease gene homologue in yeast provides copper to a ceruloplasmin-like oxidase required for iron uptake, Proc. Natl. Acad. Sci. USA 92:2632–2636.
Zhou, B. and Gitschier, J., 1997, hCTRl: a human gene for copper uptake identified by complementation in yeast, Proc. Natl. Acad. Sci. USA 94:7481–7486.
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© 2002 Kluwer Academic Publishers
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Lee, J., Thiele, D.J. (2002). Regulation and Function of the Copper Ion Transport Machinery. In: Roussel, A.M., Anderson, R.A., Favier, A.E. (eds) Trace Elements in Man and Animals 10. Springer, New York, NY. https://doi.org/10.1007/0-306-47466-2_3
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DOI: https://doi.org/10.1007/0-306-47466-2_3
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