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Regulation and Function of the Copper Ion Transport Machinery

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Trace Elements in Man and Animals 10
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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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • DiDonato, M. and Sarkar, B., 1997, Copper transport and its alterations in Menkes and Wilson diseases, Biochem. Biophy. Acta 1360:3–16.

    Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Halliwell, B. and Gutteridge, J.M.C., 1984, Oxygen toxicity, oxygen radicals, transition metals and disease, Biochem. J. 219:1–14.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Linder, M.C., 1991, Biochemistry of copper, Plenum Press, New York.

    Book  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

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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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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-306-46378-5

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