title: Biochemical characterization of the human copper transporter Ctr1.
abstract: 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 (64)Cu 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.
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0606, USA.
authors.forename: Jaekwon
authors.initials: J
authors.lastname: Lee
authors.forename: Maria Marjorette O
authors.initials: MM
authors.lastname: Peña
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nose
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Thiele
mesh_terms: D001704:Biopolymers; D027682:Cation Transport Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D000079923:Copper Transporter 1; D019084:Fluorescent Antibody Technique, Indirect; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000378:metabolism*; D016366:Open Reading Frames; D011188:Potassium / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D001704:Biopolymers; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D008565:Membrane Proteins; D011994:Recombinant Proteins; C490079:SLC31A1 protein, human; D003300:Copper; D012964:Sodium; D011188:Potassium