|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 6, 4380-4387, February 8, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Biological Chemistry, University of Michigan
Medical School, Ann Arbor, Michigan 48109-0606
The trace metal copper is an essential
cofactor for a number of biological processes including mitochondrial
oxidative phosphorylation, free radical detoxification,
neurotransmitter synthesis and maturation, and iron metabolism.
Consequently, copper transport at the cell surface and the delivery of
copper to intracellular proteins are critical events in normal
physiology. Little is known about the molecules and biochemical
mechanisms responsible for copper uptake at the plasma membrane in
mammals. Here, we demonstrate that human Ctr1 (hCtr1) is a component of
the copper transport machinery at the plasma membrane. hCtr1 transports
copper with high affinity in a time-dependent and saturable
manner and is metal-specific. hCtr1-mediated 64Cu
transport is an energy-independent process and is stimulated by
extracellular acidic pH and high K+ concentrations. hCtr1
exists as a homomultimer at the plasma membrane in mammalian cells.
This is the first report on the biochemical characterization of the
human copper transporter hCtr1, which is important for understanding
mechanisms for mammalian copper transport at the plasma membrane.
Biochemical Characterization of the Human Copper
Transporter Ctr1*
,
*
This work was supported by National Institutes of Health
Grant GM62555 and a grant from the International Copper Association (to
D. J. T.), National Institutes of Health Postdoctoral Fellowship 5F32GM18089 (to M. M. O. P.), and American Heart Association
Postdoctoral Fellowship 9920536 (to J. L.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Dept. of Biological Sciences, 705 Coker Life
Sciences Bldg., University of South Carolina, Columbia, SC 29208.
§
To whom correspondence should be addressed: Dept. of
Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606. Tel.: 734-763-5717; Fax: 734-763-7799; E-mail: dthiele@umich.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. H. Ansede, M. R. Wright, R. L. St. Claire III, R. W. Hart, H. A. Gefroh, and K. R. Brouwer Characterization of Sandwich-Cultured Hepatocytes As an in Vitro Model to Assess the Hepatobiliary Disposition of Copper Drug Metab. Dispos., May 1, 2009; 37(5): 969 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. De Feo, S. G. Aller, G. S. Siluvai, N. J. Blackburn, and V. M. Unger Three-dimensional structure of the human copper transporter hCTR1 PNAS, March 17, 2009; 106(11): 4237 - 4242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Page, J. Kropat, P. P. Hamel, and S. S. Merchant Two Chlamydomonas CTR Copper Transporters with a Novel Cys-Met Motif Are Localized to the Plasma Membrane and Function in Copper Assimilation PLANT CELL, March 1, 2009; 21(3): 928 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wu, D. Sinani, H. Kim, and J. Lee Copper Transport Activity of Yeast Ctr1 Is Down-regulated via Its C Terminus in Response to Excess Copper J. Biol. Chem., February 13, 2009; 284(7): 4112 - 4122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kim, H.-Y. Son, S. M. Bailey, and J. Lee Deletion of hepatic Ctr1 reveals its function in copper acquisition and compensatory mechanisms for copper homeostasis Am J Physiol Gastrointest Liver Physiol, February 1, 2009; 296(2): G356 - G364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Craig, M. Galus, C. M. Wood, and G. B. McClelland Dietary iron alters waterborne copper-induced gene expression in soft water acclimated zebrafish (Danio rerio) Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R362 - R373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Turski and D. J. Thiele New Roles for Copper Metabolism in Cell Proliferation, Signaling, and Disease J. Biol. Chem., January 9, 2009; 284(2): 717 - 721. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Lonnerdal Intestinal regulation of copper homeostasis: a developmental perspective Am. J. Clinical Nutrition, September 1, 2008; 88(3): 846S - 850S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Moriya, Y.-H. Ho, A. Grana, L. Nguyen, A. Alvarez, R. Jamil, M. L. Ackland, A. Michalczyk, P. Hamer, D. Ramos, et al. Copper is taken up efficiently from albumin and {alpha}2-macroglobulin by cultured human cells by more than one mechanism Am J Physiol Cell Physiol, September 1, 2008; 295(3): C708 - C721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Abdul Jalil, V. Ritz, A. Jakimenko, C. Schmitz-Salue, H. Siebert, D. Awuah, A. Kotthaus, T. Kietzmann, C. Ziemann, and K. I. Hirsch-Ernst Vesicular localization of the rat ATP-binding cassette half-transporter rAbcb6 Am J Physiol Cell Physiol, February 1, 2008; 294(2): C579 - C590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sinani, D. J. Adle, H. Kim, and J. Lee Distinct Mechanisms for Ctr1-mediated Copper and Cisplatin Transport J. Biol. Chem., September 14, 2007; 282(37): 26775 - 26785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Zimnicka, E. B. Maryon, and J. H. Kaplan Human Copper Transporter hCTR1 Mediates Basolateral Uptake of Copper into Enterocytes: IMPLICATIONS FOR COPPER HOMEOSTASIS J. Biol. Chem., September 7, 2007; 282(36): 26471 - 26480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Turski and D. J. Thiele Drosophila Ctr1A Functions as a Copper Transporter Essential for Development J. Biol. Chem., August 17, 2007; 282(33): 24017 - 24026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Rees and D. J. Thiele Identification of a Vacuole-associated Metalloreductase and Its Role in Ctr2-mediated Intracellular Copper Mobilization J. Biol. Chem., July 27, 2007; 282(30): 21629 - 21638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Maryon, S. A. Molloy, and J. H. Kaplan O-Linked Glycosylation at Threonine 27 Protects the Copper Transporter hCTR1 from Proteolytic Cleavage in Mammalian Cells J. Biol. Chem., July 13, 2007; 282(28): 20376 - 20387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Lopez-Serrano, F. Solano, and A. Sanchez-Amat Involvement of a novel copper chaperone in tyrosinase activity and melanin synthesis in Marinomonas mediterranea Microbiology, July 1, 2007; 153(7): 2241 - 2249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lutsenko, N. L. Barnes, M. Y. Bartee, and O. Y. Dmitriev Function and Regulation of Human Copper-Transporting ATPases Physiol Rev, July 1, 2007; 87(3): 1011 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Thwaites and C. M. H. Anderson H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine Exp Physiol, July 1, 2007; 92(4): 603 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Kelleher and B. Lonnerdal Mammary gland copper transport is stimulated by prolactin through alterations in Ctr1 and Atp7A localization Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R1181 - R1191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Holzer, N. M. Varki, Q. T. Le, M. A. Gibson, P. Naredi, and S. B. Howell Expression of the Human Copper Influx Transporter 1 in Normal and Malignant Human Tissues J. Histochem. Cytochem., September 1, 2006; 54(9): 1041 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Aller and V. M. Unger Projection structure of the human copper transporter CTR1 at 6-A resolution reveals a compact trimer with a novel channel-like architecture PNAS, March 7, 2006; 103(10): 3627 - 3632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-M. Kuo, A. A. Gybina, J. W. Pyatskowit, J. Gitschier, and J. R. Prohaska Copper Transport Protein (Ctr1) Levels in Mice Are Tissue Specific and Dependent on Copper Status J. Nutr., January 1, 2006; 136(1): 21 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Eisses and J. H. Kaplan The Mechanism of Copper Uptake Mediated by Human CTR1: A MUTATIONAL ANALYSIS J. Biol. Chem., November 4, 2005; 280(44): 37159 - 37168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Bauerly, S. L. Kelleher, and B. Lonnerdal Effects of copper supplementation on copper absorption, tissue distribution, and copper transporter expression in an infant rat model Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G1007 - G1014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Eisses, Y. Chi, and J. H. Kaplan Stable Plasma Membrane Levels of hCTR1 Mediate Cellular Copper Uptake J. Biol. Chem., March 11, 2005; 280(10): 9635 - 9639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Burke and R. D. Handy Sodium-sensitive and -insensitive copper accumulation by isolated intestinal cells of rainbow trout Oncorhynchus mykiss J. Exp. Biol., January 15, 2005; 208(2): 391 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Hanigan, M. Deng, L. Zhang, P. T. Taylor Jr., and M. G. Lapus Stress response inhibits the nephrotoxicity of cisplatin Am J Physiol Renal Physiol, January 1, 2005; 288(1): F125 - F132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Aller, E. T. Eng, C. J. De Feo, and V. M. Unger Eukaryotic CTR Copper Uptake Transporters Require Two Faces of the Third Transmembrane Domain for Helix Packing, Oligomerization, and Function J. Biol. Chem., December 17, 2004; 279(51): 53435 - 53441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Guo, K. Smith, and M. J. Petris Cisplatin Stabilizes a Multimeric Complex of the Human Ctr1 Copper Transporter: REQUIREMENT FOR THE EXTRACELLULAR METHIONINE-RICH CLUSTERS J. Biol. Chem., November 5, 2004; 279(45): 46393 - 46399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Holzer, G. Samimi, K. Katano, W. Naerdemann, X. Lin, R. Safaei, and S. B. Howell The Copper Influx Transporter Human Copper Transport Protein 1 Regulates the Uptake of Cisplatin in Human Ovarian Carcinoma Cells Mol. Pharmacol., October 1, 2004; 66(4): 817 - 823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Holzer, K. Katano, L. W. J. Klomp, and S. B. Howell Cisplatin Rapidly Down-regulates Its Own Influx Transporter hCTR1 in Cultured Human Ovarian Carcinoma Cells Clin. Cancer Res., October 1, 2004; 10(19): 6744 - 6749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Arredondo, V. Cambiazo, L. Tapia, M. Gonzalez-Aguero, M. T. Nunez, R. Uauy, and M. Gonzalez Copper overload affects copper and iron metabolism in Hep-G2 cells Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G27 - G32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Shingles, L. E. Wimmers, and R. E. McCarty Copper Transport Across Pea Thylakoid Membranes Plant Physiology, May 1, 2004; 135(1): 145 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Guo, K. Smith, J. Lee, D. J. Thiele, and M. J. Petris Identification of Methionine-rich Clusters That Regulate Copper-stimulated Endocytosis of the Human Ctr1 Copper Transporter J. Biol. Chem., April 23, 2004; 279(17): 17428 - 17433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Prudovsky, A. Mandinova, R. Soldi, C. Bagala, I. Graziani, M. Landriscina, F. Tarantini, M. Duarte, S. Bellum, H. Doherty, et al. The non-classical export routes: FGF1 and IL-1{alpha} point the way J. Cell Sci., December 15, 2003; 116(24): 4871 - 4881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhou, K. M. Cadigan, and D. J. Thiele A Copper-regulated Transporter Required for Copper Acquisition, Pigmentation, and Specific Stages of Development in Drosophila melanogaster J. Biol. Chem., November 28, 2003; 278(48): 48210 - 48218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J Troost, R.-J. M Brummer, J. R Dainty, J. A Hoogewerff, V. J Bull, and W. H. Saris Iron supplements inhibit zinc but not copper absorption in vivo in ileostomy subjects Am. J. Clinical Nutrition, November 1, 2003; 78(5): 1018 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Katano, R. Safaei, G. Samimi, A. Holzer, M. Rochdi, and S. B. Howell The Copper Export Pump ATP7B Modulates the Cellular Pharmacology of Carboplatin in Ovarian Carcinoma Cells Mol. Pharmacol., August 1, 2003; 64(2): 466 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Kelleher and B. Lonnerdal Marginal Maternal Zn Intake in Rats Alters Mammary Gland Cu Transporter Levels and Milk Cu Concentration and Affects Neonatal Cu Metabolism J. Nutr., July 1, 2003; 133(7): 2141 - 2148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Zerounian, C. Redekosky, R. Malpe, and M. C. Linder Regulation of copper absorption by copper availability in the Caco-2 cell intestinal model Am J Physiol Gastrointest Liver Physiol, May 1, 2003; 284(5): G739 - G747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Thiele Integrating Trace Element Metabolism from the Cell to the Whole Organism J. Nutr., May 1, 2003; 133(5): 1579S - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Arnesano, L. Banci, I. Bertini, S. Mangani, and A. R. Thompsett Bioinorganic Chemistry Special Feature: A redox switch in CopC: An intriguing copper trafficking protein that binds copper(I) and copper(II) at different sites PNAS, April 1, 2003; 100(7): 3814 - 3819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Rachidi, D. Vilette, P. Guiraud, M. Arlotto, J. Riondel, H. Laude, S. Lehmann, and A. Favier Expression of Prion Protein Increases Cellular Copper Binding and Antioxidant Enzyme Activities but Not Copper Delivery J. Biol. Chem., March 7, 2003; 278(11): 9064 - 9072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Petris, K. Smith, J. Lee, and D. J. Thiele Copper-stimulated Endocytosis and Degradation of the Human Copper Transporter, hCtr1 J. Biol. Chem., March 7, 2003; 278(11): 9639 - 9646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Steveson, G. D. Ciccotosto, X.-M. Ma, G. P. Mueller, R. E. Mains, and B. A. Eipper Menkes Protein Contributes to the Function of Peptidylglycine {alpha}-Amidating Monooxygenase Endocrinology, January 1, 2003; 144(1): 188 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Bury, P. A. Walker, and C. N. Glover Nutritive metal uptake in teleost fish J. Exp. Biol., January 1, 2003; 206(1): 11 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Bellemare, L. Shaner, K. A. Morano, J. Beaudoin, R. Langlois, and S. Labbe Ctr6, a Vacuolar Membrane Copper Transporter in Schizosaccharomyces pombe J. Biol. Chem., November 22, 2002; 277(48): 46676 - 46686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ishida, J. Lee, D. J. Thiele, and I. Herskowitz From the Cover: Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals PNAS, October 29, 2002; 99(22): 14298 - 14302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Eisses and J. H. Kaplan Molecular Characterization of hCTR1, the Human Copper Uptake Protein J. Biol. Chem., August 2, 2002; 277(32): 29162 - 29171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Puig, J. Lee, M. Lau, and D. J. Thiele Biochemical and Genetic Analyses of Yeast and Human High Affinity Copper Transporters Suggest a Conserved Mechanism for Copper Uptake J. Biol. Chem., July 12, 2002; 277(29): 26021 - 26030. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |