Experts and Doctors on cation transport proteins in Salt Lake City, Utah, United States

Summary

Locale: Salt Lake City, Utah, United States
Topic: cation transport proteins

Top Publications

  1. Li L, Kaplan J, Ward D. The glucose sensor Snf1 and the transcription factors Msn2 and Msn4 regulate transcription of the vacuolar iron importer gene CCC1 and iron resistance in yeast. J Biol Chem. 2017;292:15577-15586 pubmed publisher
    ..In conclusion, we show that yeast have developed multiple transcriptional mechanisms to regulate Ccc1 expression and to protect against high cytosolic iron toxicity. ..
  2. De Domenico I, Ward D, di Patti M, Jeong S, David S, Musci G, et al. Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin. EMBO J. 2007;26:2823-31 pubmed
    ..The requirement for a ferroxidase to maintain iron transport activity represents a new mechanism of regulating cellular iron export, a new function for Cp and an explanation for brain iron overload in patients with aceruloplasminemia. ..
  3. Zou A, Xu Q, Sanguinetti M. A mutation in the pore region of HERG K+ channels expressed in Xenopus oocytes reduces rectification by shifting the voltage dependence of inactivation. J Physiol. 1998;509 ( Pt 1):129-37 pubmed
    ..0 pS between +40 and +100 mV (120 mM extracellular K+). This compares to a gamma of 12.1 and 5.1 pS for WT-HERG channels under the same conditions. ..
  4. Fernandez D, Ghanta A, Kauffman G, Sanguinetti M. Physicochemical features of the HERG channel drug binding site. J Biol Chem. 2004;279:10120-7 pubmed
    ..Together, these findings assign specific residues to receptor fields predicted by pharmacophore models of hERG channel blockers and provide a refined molecular understanding of the drug binding site. ..
  5. Sanguinetti M, Xu Q. Mutations of the S4-S5 linker alter activation properties of HERG potassium channels expressed in Xenopus oocytes. J Physiol. 1999;514 ( Pt 3):667-75 pubmed
    ..5. The results indicate that the S4-S5 linker is a crucial component of the activation gate of HERG channels. ..
  6. Mitcheson J, Chen J, Sanguinetti M. Trapping of a methanesulfonanilide by closure of the HERG potassium channel activation gate. J Gen Physiol. 2000;115:229-40 pubmed
    ..The ability of HERG channels to trap MK-499, despite its large size, suggests that the vestibule of this channel is larger than the well studied Shaker K(+) channel. ..
  7. Etheridge S, Compton S, Tristani Firouzi M, Mason J. A new oral therapy for long QT syndrome: long-term oral potassium improves repolarization in patients with HERG mutations. J Am Coll Cardiol. 2003;42:1777-82 pubmed
    ..This can be achieved safely and results in improvement in repolarization. Further studies are warranted to determine whether this will reduce the incidence of life-threatening events in LQTS patients. ..
  8. Heaton D, Nittis T, Srinivasan C, Winge D. Mutational analysis of the mitochondrial copper metallochaperone Cox17. J Biol Chem. 2000;275:37582-7 pubmed
    ..Thus, only three cysteinyl residues are important for the ligation of three Cu(I) ions. A novel mode of Cu(I) binding is predicted. ..
  9. Mitcheson J, Chen J, Lin M, Culberson C, Sanguinetti M. A structural basis for drug-induced long QT syndrome. Proc Natl Acad Sci U S A. 2000;97:12329-33 pubmed
    ..These findings suggest a possible structural explanation for how so many commonly used medications block HERG but not other Kv channels and should facilitate the rational design of drugs devoid of HERG channel binding activity. ..

More Information

Publications40

  1. De Domenico I, Vaughn M, Yoon D, Kushner J, Ward D, Kaplan J. Zebrafish as a model for defining the functional impact of mammalian ferroportin mutations. Blood. 2007;110:3780-3 pubmed
    ..Expression of wild-type ferroportin or hepcidin-resistant ferroportin (N144H) does not affect erythropoiesis. Zebrafish provides a facile way of identifying which ferroportin mutants may lead to macrophage iron loading. ..
  2. Srinivasan C, Posewitz M, George G, Winge D. Characterization of the copper chaperone Cox17 of Saccharomyces cerevisiae. Biochemistry. 1998;37:7572-7 pubmed
    ..26 A, plus a short Cu-Cu distance of 2.7 A, indicating a binuclear cluster in Cox17. The cuprous-thiolate cluster in Cox17 is substantially more labile than structurally related clusters in metallothioneins. ..
  3. Romney S, Newman B, Thacker C, Leibold E. HIF-1 regulates iron homeostasis in Caenorhabditis elegans by activation and inhibition of genes involved in iron uptake and storage. PLoS Genet. 2011;7:e1002394 pubmed publisher
    ..These data show that HIF-1 regulates intestinal iron homeostasis during iron deficiency by activating and inhibiting genes involved in iron uptake and storage. ..
  4. Gawenis L, Bradford E, Alper S, Prasad V, Shull G. AE2 Cl-/HCO3- exchanger is required for normal cAMP-stimulated anion secretion in murine proximal colon. Am J Physiol Gastrointest Liver Physiol. 2010;298:G493-503 pubmed publisher
    ..These results show that AE2 is a component of the basolateral ion transport mechanisms that support anion secretion in the proximal colon. ..
  5. Horng Y, Cobine P, Maxfield A, Carr H, Winge D. Specific copper transfer from the Cox17 metallochaperone to both Sco1 and Cox11 in the assembly of yeast cytochrome C oxidase. J Biol Chem. 2004;279:35334-40 pubmed
    ..Metallation of these domains was strictly dependent on the co-expression of Cox17. Thus, Cox17 represents a novel copper chaperone that delivers copper to two proteins. ..
  6. Paradkar P, De Domenico I, Durchfort N, Zohn I, Kaplan J, Ward D. Iron depletion limits intracellular bacterial growth in macrophages. Blood. 2008;112:866-74 pubmed publisher
  7. Rigby K, Zhang L, Cobine P, George G, Winge D. characterization of the cytochrome c oxidase assembly factor Cox19 of Saccharomyces cerevisiae. J Biol Chem. 2007;282:10233-42 pubmed
    ..Cysteinyl residues important for Cu(I) binding are also shown to be important for the in vivo function of Cox19. Thus, a correlation exists in the ability to bind Cu(I) and in vivo function. ..
  8. De Domenico I, Ward D, Langelier C, Vaughn M, Nemeth E, Sundquist W, et al. The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell. 2007;18:2569-78 pubmed
    ..Depletion of proteins involved in multivesicular body trafficking (Endosome Sorting Complex Required for Transport proteins), by small-interfering RNA, reduces the trafficking of Fpn-green fluorescent to the lysosome. ..
  9. Li L, Kaplan J. The yeast gene MSC2, a member of the cation diffusion facilitator family, affects the cellular distribution of zinc. J Biol Chem. 2001;276:5036-43 pubmed
    ..An epitope-tagged Msc2p was localized to the endoplasmic reticulum/nucleus. These results suggest that Msc2p affects the cellular distribution of zinc and, in particular, the zinc content of nuclei. ..
  10. Heaton D, George G, Garrison G, Winge D. The mitochondrial copper metallochaperone Cox17 exists as an oligomeric, polycopper complex. Biochemistry. 2001;40:743-51 pubmed
    ..Thus, the oligomeric state of Cox17 may be important to its physiological function. ..
  11. De Domenico I, Zhang T, Koening C, Branch R, London N, Lo E, et al. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J Clin Invest. 2010;120:2395-405 pubmed publisher
    ..The results of our study suggest a new function for hepcidin in modulating acute inflammatory responses. ..
  12. De Domenico I, Lo E, Ward D, Kaplan J. Human mutation D157G in ferroportin leads to hepcidin-independent binding of Jak2 and ferroportin down-regulation. Blood. 2010;115:2956-9 pubmed publisher
    ..These results identify a hepcidin-independent regulation of Fpn that can result in alterations in iron homeostasis. ..
  13. Troadec M, Ward D, Lo E, Kaplan J, De Domenico I. Induction of FPN1 transcription by MTF-1 reveals a role for ferroportin in transition metal efflux. Blood. 2010;116:4657-64 pubmed publisher
    ..We demonstrate that Fpn can transport zinc and can protect zinc sensitive cells from high zinc toxicity. ..
  14. De Domenico I, Lo E, Ward D, Kaplan J. Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2. Proc Natl Acad Sci U S A. 2009;106:3800-5 pubmed publisher
    ..These results provide a molecular explanation for the dominant inheritance of hepcidin resistant iron overload disease. ..
  15. Lin H, Kumanovics A, Nelson J, Warner D, Ward D, Kaplan J. A single amino acid change in the yeast vacuolar metal transporters ZRC1 and COT1 alters their substrate specificity. J Biol Chem. 2008;283:33865-73 pubmed publisher
    ..These mutations are within the second hydrophobic domain of the transporters and show the essential nature of this domain in the specificity of metal transport. ..
  16. Curran M, Splawski I, Timothy K, Vincent G, Green E, Keating M. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995;80:795-803 pubmed
    ..In one kindred, the mutation arose de novo. Northern blot analyses show that HERG is strongly expressed in the heart. These data indicate that HERG is LQT2 and suggest a likely cellular mechanism for torsade de pointes. ..
  17. Kumanovics A, Poruk K, Osborn K, Ward D, Kaplan J. YKE4 (YIL023C) encodes a bidirectional zinc transporter in the endoplasmic reticulum of Saccharomyces cerevisiae. J Biol Chem. 2006;281:22566-74 pubmed
  18. Ardon O, Bussey H, Philpott C, Ward D, Davis Kaplan S, Verroneau S, et al. Identification of a Candida albicans ferrichrome transporter and its characterization by expression in Saccharomyces cerevisiae. J Biol Chem. 2001;276:43049-55 pubmed
  19. Li L, Bagley D, Ward D, Kaplan J. Yap5 is an iron-responsive transcriptional activator that regulates vacuolar iron storage in yeast. Mol Cell Biol. 2008;28:1326-37 pubmed
    ..These results show that Yap5 is an iron-sensing transcription factor and that iron regulates transcriptional activation. ..
  20. De Domenico I, Ward D, Musci G, Kaplan J. Evidence for the multimeric structure of ferroportin. Blood. 2007;109:2205-9 pubmed
    ..These results support the hypothesis that the dominant inheritance of Fpn-iron overload disease is due to the dominant-negative effects of mutant Fpn proteins. ..
  21. Li L, Kaplan J. A mitochondrial-vacuolar signaling pathway in yeast that affects iron and copper metabolism. J Biol Chem. 2004;279:33653-61 pubmed
    ..These results suggest that deletion of mitochondrial proteins can alter vacuolar metal homeostasis. The data also indicate that increased expression of the AFT1-regulated gene(s) can disrupt copper homeostasis. ..
  22. Lin H, Burton D, Li L, Warner D, Phillips J, Ward D, et al. Gain-of-function mutations identify amino acids within transmembrane domains of the yeast vacuolar transporter Zrc1 that determine metal specificity. Biochem J. 2009;422:273-83 pubmed publisher
    ..These results suggest that substrate selection involves co-operativity between transmembrane domains. ..
  23. Bird A, Blankman E, Stillman D, Eide D, Winge D. The Zap1 transcriptional activator also acts as a repressor by binding downstream of the TATA box in ZRT2. EMBO J. 2004;23:1123-32 pubmed
    ..These results indicate that the unusual pattern of ZRT2 regulation among Zap1 target genes involves the antagonistic effect of Zap1 binding to a low-affinity ZRE repressor site and high-affinity ZREs required for activation. ..
  24. Li L, Murdock G, Bagley D, Jia X, Ward D, Kaplan J. Genetic dissection of a mitochondria-vacuole signaling pathway in yeast reveals a link between chronic oxidative stress and vacuolar iron transport. J Biol Chem. 2010;285:10232-42 pubmed publisher
    ..These results suggest that mitochondria-induced oxidant damage is responsible for activating Ccc1 and that Fra1 and Tsa1 can reduce oxidant damage. ..
  25. Li L, Chen O, McVey Ward D, Kaplan J. CCC1 is a transporter that mediates vacuolar iron storage in yeast. J Biol Chem. 2001;276:29515-9 pubmed
    ..These results indicate that yeast can store iron in the vacuole and that CCC1 is involved in the transfer of iron from the cytosol to the vacuole. ..
  26. Chen O, Kaplan J. CCC1 suppresses mitochondrial damage in the yeast model of Friedreich's ataxia by limiting mitochondrial iron accumulation. J Biol Chem. 2000;275:7626-32 pubmed
    ..Although the mechanism by which CCC1 expression affects cytosolic iron is not known, the data suggest that excessive mitochondrial iron accumulation only occurs when cytosolic free iron levels are high. ..
  27. Gabrielsen J, Gao Y, Simcox J, Huang J, Thorup D, Jones D, et al. Adipocyte iron regulates adiponectin and insulin sensitivity. J Clin Invest. 2012;122:3529-40 pubmed publisher
    ..These findings demonstrate a causal role for iron as a risk factor for metabolic syndrome and a role for adipocytes in modulating metabolism through adiponectin in response to iron stores. ..
  28. Buck Koehntop B, Defossez P. On how mammalian transcription factors recognize methylated DNA. Epigenetics. 2013;8:131-7 pubmed publisher
    ..These fresh insights have consequences for the analysis of the many other zinc finger proteins present in the genome, and for the biology of methyl-CpG binding zinc finger proteins. ..
  29. Rigby K, Cobine P, Khalimonchuk O, Winge D. Mapping the functional interaction of Sco1 and Cox2 in cytochrome oxidase biogenesis. J Biol Chem. 2008;283:15015-22 pubmed publisher
    ..In addition, the mutants failed to suppress the hydrogen peroxide sensitivity of sco1Delta cells. These studies implicate different surfaces on Sco1 for interaction or function with Cox17 and Cox2. ..
  30. Li L, Kaplan J. Characterization of two homologous yeast genes that encode mitochondrial iron transporters. J Biol Chem. 1997;272:28485-93 pubmed
    ..These results suggest that the mitochondria may act as a reservoir for iron that can be mobilized and used for cytosolic purposes. ..
  31. Sanguinetti M, Jiang C, Curran M, Keating M. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell. 1995;81:299-307 pubmed
    ..Since block of IKr is a known mechanism for drug-induced cardiac arrhythmias, the finding that HERG encodes IKr channels provides a mechanistic link between certain forms of inherited and acquired LQT. ..