title: Potassium and the K+/H+ Exchanger Kha1p Promote Binding of Copper to ApoFet3p Multi-copper Ferroxidase.
abstract: Acquisition and distribution of metal ions support a number of biological processes. Here we show that respiratory growth of and iron acquisition by the yeast Saccharomyces cerevisiae relies on potassium (K(+)) compartmentalization to the trans-Golgi network via Kha1p, a K(+)/H(+) exchanger. K(+) in the trans-Golgi network facilitates binding of copper to the Fet3p multi-copper ferroxidase. The effect of K(+) is not dependent on stable binding with Fet3p or alteration of the characteristics of the secretory pathway. The data suggest that K(+) acts as a chemical factor in Fet3p maturation, a role similar to that of cations in folding of nucleic acids. Up-regulation of KHA1 gene in response to iron limitation via iron-specific transcription factors indicates that K(+) compartmentalization is linked to cellular iron homeostasis. Our study reveals a novel functional role of K(+) in the binding of copper to apoFet3p and identifies a K(+)/H(+) exchanger at the secretory pathway as a new molecular factor associated with iron uptake in yeast.
authors.affiliation: From the Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0664, College of Life and Environmental Sciences, Shanghai Normal University, Shanghai, China 200234.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wu
authors.affiliation: From the Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0664.
authors.forename: Heejeong
authors.initials: H
authors.lastname: Kim
authors.affiliation: From the Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0664.
authors.forename: Javier
authors.initials: J
authors.lastname: Seravalli
authors.affiliation: From the Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0664.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Barycki
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229-3900.
authors.forename: P John
authors.initials: PJ
authors.lastname: Hart
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri 63104.
authors.forename: David W
authors.initials: DW
authors.lastname: Gohara
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri 63104.
authors.forename: Enrico
authors.initials: E
authors.lastname: Di Cera
authors.affiliation: Department of Systems Biotechnology, Chung-Ang University, Anseong, Korea 456-756, and.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Jung
authors.affiliation: Department of Biochemistry, University at Buffalo, Buffalo, New York 14214-3000.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kosman
authors.affiliation: From the Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0664, jlee7@unl.edu.
authors.forename: Jaekwon
authors.initials: J
authors.lastname: Lee
mesh_terms: D002570:Ceruloplasmin / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D007501:Iron; D011188:Potassium / Q000378:metabolism; D027961:Potassium-Hydrogen Antiporters / Q000096:biosynthesis* / Q000235:genetics; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C421963:KHA1 protein, S cerevisiae; D027961:Potassium-Hydrogen Antiporters; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper; D007501:Iron; D002570:Ceruloplasmin; C085513:FET3 protein, S cerevisiae; D011188:Potassium
keywords: copper; ferroxidase; iron; iron response element (IRE); potassium transport; protein secretion