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Mammalian copper homeostasis requires retromer-dependent recycling of the high-affinity copper transporter 1
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Abstract
The concentration of essential micronutrients, such as copper (used here to describe both Cu+ and Cu2+), within the cell is tightly regulated to avoid their adverse deficiency and toxicity effects. Retromer-mediated sorting and recycling of nutrient transporters within the endo-lysosomal network is an essential process in regulating nutrient balance. Cellular copper homeostasis is regulated primarily by two transporters: the copper influx transporter copper transporter 1 (CTR1; also known as SLC31A1), which controls the uptake of copper, and the copper-extruding ATPase ATP7A, a recognised retromer cargo. Here, we show that in response to fluctuating extracellular copper, retromer controls the delivery of CTR1 to the cell surface. Following copper exposure, CTR1 is endocytosed to prevent excessive copper uptake. We reveal that internalised CTR1 localises on retromer-positive endosomes and, in response to decreased extracellular copper, retromer controls the recycling of CTR1 back to the cell surface to maintain copper homeostasis. In addition to copper, CTR1 plays a central role in the trafficking of platinum. The efficacy of platinum-based cancer drugs has been correlated with CTR1 expression. Consistent with this, we demonstrate that retromer-deficient cells show reduced sensitivity to the platinum-based drug cisplatin.
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Expression of dominant negative RAB10(T23N) in wild-type HeLa cells reduced steady-state surface levels of Retromer cargoes GLUT1, KIDINS220, and the copper-dependent cell surface recycling of CTR1.
“Finally, we lentivirally expressed dominant negative RAB10(T23N) in wild-type HeLa cells. This revealed a reduced steady-state surface level of Retromer cargoes GLUT1, KIDINS220 and the copper-dependent cell surface recycling of CTR1108 (Fig. 5E, F).”
From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [108]
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Retromer: A Master Conductor of Endosome Sorting
Burd, C., & Cullen, P. J. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016774 · Cited by 435
Self-citationRetriever is a multiprotein complex for retromer-independent endosomal cargo recycling
McNally, K. E., Faulkner, R., Steinberg, F., Gallon, M., Ghai, R., Pim, D., Langton, P., Pearson, N., Danson, C. M., Nägele, H., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3610 · Cited by 346
Self-citationEndosomal retrieval of cargo: Retromer is not alone
McNally, K. E., & Cullen, P. J. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.06.005 · Cited by 169
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Research works printed but not linked: 77
- Arighi, 2004, Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor, J. Cell Biol., 165, 123, 10.1083/jcb.200312055 · DOI · Paper page
- Bai, 2012, Mechanistic insights into regulated cargo binding by ACAP1 protein, J. Biol. Chem., 287, 28675, 10.1074/jbc.M112.378810 · DOI
- Berridge, 2005, Tetrazolium dyes as tools in cell biology: New insights into their cellular reduction, Biotechnol. Annu. Rev., 11, 127, 10.1016/S1387-2656(05)11004-7 · DOI · Paper page
- Bompiani, 2016, Copper transporters and chaperones CTR1, CTR2, ATOX1, and CCS as determinants of cisplatin sensitivity, Metallomics, 8, 951, 10.1039/C6MT00076B · DOI
- Clairfeuille, 2016, A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex, Nat. Struct. Mol. Biol., 23, 921, 10.1038/nsmb.3290 · DOI · Paper page
- Clifford, 2016, Dynamic internalization and recycling of a metal ion transporter: Cu homeostasis and CTR1, the human Cu+ uptake system, J. Cell Sci., 129, 1711, 10.1242/jcs.173351 · DOI
- Corvera, 1986, Mechanism of receptor kinase action on membrane protein recycling, Ann. N. Y. Acad. Sci., 488, 419, 10.1111/j.1749-6632.1986.tb46575.x · DOI
- Cosaert, 2002, Platinum drugs in the treatment of non-small-cell lung cancer, Br. J. Cancer, 87, 825, 10.1038/sj.bjc.6600540 · DOI
- Cullen, 2018, To degrade or not to degrade: mechanisms and significance of endocytic recycling, Nat. Rev. Mol. Cell Biol., 19, 679, 10.1038/s41580-018-0053-7 · DOI · Paper page
- Curnock, 2019, TFEB controls retromer expression in response to nutrient availability, J. Cell Biol., 218, 3954, 10.1083/jcb.201903006 · DOI · Paper page
- Dancis, 1994, Molecular characterization of a copper transport protein in S. cerevisiae: an unexpected role for copper in iron transport, Cell, 76, 393, 10.1016/0092-8674(94)90345-X · DOI · Paper page
- Daniel, 2004, Copper storage diseases: Menkes, Wilson's, and cancer, Front. Biosci., 9, 2652, 10.2741/1424 · DOI
- de Bie, 2007, Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes, J. Med. Genet., 44, 673, 10.1136/jmg.2007.052746 · DOI
- Derivery, 2009, The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex, Dev. Cell, 17, 712, 10.1016/j.devcel.2009.09.010 · DOI · Paper page
- Dolgova, 2009, The soluble metal-binding domain of the copper transporter ATP7B binds and detoxifies cisplatin, Biochem. J., 419, 51, 10.1042/BJ20081359 · DOI
- Eisses, 2005, The mechanism of copper uptake mediated by human CTR1: a mutational analysis, J. Biol. Chem., 280, 37159, 10.1074/jbc.M508822200 · DOI
- Gallon, 2014, A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer, Proc. Natl. Acad. Sci. USA, 111, E3604, 10.1073/pnas.1410552111 · DOI · Paper page
- Gomez, 2009, A FAM21-containing WASH complex regulates retromer-dependent sorting, Dev. Cell, 17, 699, 10.1016/j.devcel.2009.09.009 · DOI · Paper page
- Grant, 2009, Pathways and mechanisms of endocytic recycling, Nat. Rev. Mol. Cell Biol., 10, 597, 10.1038/nrm2755 · DOI · Paper page
- Guo, 2004, Identification of methionine-rich clusters that regulate copper-stimulated endocytosis of the human Ctr1 copper transporter, J. Biol. Chem., 279, 17428, 10.1074/jbc.M401493200 · DOI
- Gupta, 2009, Human copper transporters: mechanism, role in human diseases and therapeutic potential, Future Med. Chem., 1, 1125, 10.4155/fmc.09.84 · DOI
- Hamza, 1999, Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis, Proc. Natl. Acad. Sci. USA, 96, 13363, 10.1073/pnas.96.23.13363 · DOI
- Harbour, 2012, Recruitment of the endosomal WASH complex is mediated by the extended ‘tail’ of Fam21 binding to the retromer protein Vps35, Biochem. J., 442, 209, 10.1042/BJ20111761 · DOI · Paper page
- Hartwig, 2019, Trafficking mechanisms of P-type ATPase copper transporters, Curr. Opin. Cell Biol., 59, 24, 10.1016/j.ceb.2019.02.009 · DOI
- Holzer, 2004, The copper influx transporter human copper transport protein 1 regulates the uptake of cisplatin in human ovarian carcinoma cells, Mol. Pharmacol., 66, 817, 10.1124/mol.104.001198 · DOI
- Holzer, 2006, Contribution of the major copper influx transporter CTR1 to the cellular accumulation of cisplatin, carboplatin, and oxaliplatin, Mol. Pharmacol., 70, 1390, 10.1124/mol.106.022624 · DOI
- Howell, 2010, Copper transporters and the cellular pharmacology of the platinum-containing cancer drugs, Mol. Pharmacol., 77, 887, 10.1124/mol.109.063172 · DOI
- Hung, 1997, Biochemical characterization of the Wilson disease protein and functional expression in the yeast Saccharomyces cerevisiae, J. Biol. Chem., 272, 21461, 10.1074/jbc.272.34.21461 · DOI
- Ivy, 2013, A re-evaluation of the role of hCTR1, the human high-affinity copper transporter, in platinum-drug entry into human cells, Mol. Pharmacol., 83, 1237, 10.1124/mol.113.085068 · DOI
- Jandial, 2009, Enhanced delivery of cisplatin to intraperitoneal ovarian carcinomas mediated by the effects of bortezomib on the human copper transporter 1, Clin. Cancer Res., 15, 553, 10.1158/1078-0432.CCR-08-2081 · DOI
- Jenness, 1986, Down regulation of the alpha-factor pheromone receptor in S. cerevisiae, Cell, 46, 345, 10.1016/0092-8674(86)90655-0 · DOI
- Jia, 2012, Multiple repeat elements within the FAM21 tail link the WASH actin regulatory complex to the retromer, Mol. Biol. Cell, 23, 2352, 10.1091/mbc.e11-12-1059 · DOI · Paper page
- Jones, 2012, Regulation of membrane protein degradation by starvation-response pathways, Traffic, 13, 468, 10.1111/j.1600-0854.2011.01314.x · DOI
- Kahra, 2016, The C-terminus of human copper importer Ctr1 acts as a binding site and transfers copper to Atox1, Biophys. J., 110, 95, 10.1016/j.bpj.2015.11.016 · DOI
- Katano, 2004, Confocal microscopic analysis of the interaction between cisplatin and the copper transporter ATP7B in human ovarian carcinoma cells, Clin. Cancer Res., 10, 4578, 10.1158/1078-0432.CCR-03-0689 · DOI
- Kerr, 2005, A novel mammalian retromer component, Vps26B, Traffic, 6, 991, 10.1111/j.1600-0854.2005.00328.x · DOI · Paper page
- Kim, 2008, Mechanisms for copper acquisition, distribution and regulation, Nat. Chem. Biol., 4, 176, 10.1038/nchembio.72 · DOI
- Kim, 2014, Copper transporter CTR1 expression and tissue platinum concentration in non-small cell lung cancer, Lung Cancer, 85, 88, 10.1016/j.lungcan.2014.04.005 · DOI
- Klomp, 2002, Biochemical characterization and subcellular localization of human copper transporter 1 (hCTR1), Biochem. J., 364, 497, 10.1042/bj20011803 · DOI
- Kuo, 2001, The copper transporter CTR1 provides an essential function in mammalian embryonic development, Proc. Natl. Acad. Sci. USA, 98, 6836, 10.1073/pnas.111057298 · DOI
- Larin, 1999, Characterization of the interaction between the Wilson and Menkes disease proteins and the cytoplasmic copper chaperone, HAH1p, J. Biol. Chem., 274, 28497, 10.1074/jbc.274.40.28497 · DOI
- Larson, 2009, The role of the mammalian copper transporter 1 in the cellular accumulation of platinum-based drugs, Mol. Pharmacol., 75, 324, 10.1124/mol.108.052381 · DOI
- Larson, 2010, The role of the methionines and histidines in the transmembrane domain of mammalian copper transporter 1 in the cellular accumulation of cisplatin, Mol. Pharmacol., 78, 333, 10.1124/mol.110.064766 · DOI
- Lee, 2001, Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development, Proc. Natl. Acad. Sci. USA, 98, 6842, 10.1073/pnas.111058698 · DOI
- Lee, 2002, Biochemical characterization of the human copper transporter Ctr1, J. Biol. Chem., 277, 4380, 10.1074/jbc.M104728200 · DOI
- Lim, 2006, Copper-dependent interaction of dynactin subunit p62 with the N terminus of ATP7B but not ATP7A, J. Biol. Chem., 281, 14006, 10.1074/jbc.M512745200 · DOI
- Lim, 2006, Copper-dependent interaction of glutaredoxin with the N termini of the copper-ATPases (ATP7A and ATP7B) defective in Menkes and Wilson diseases, Biochem. Biophys. Res. Commun., 348, 428, 10.1016/j.bbrc.2006.07.067 · DOI
- Liu, 2007, Regulation of copper-dependent endocytosis and vacuolar degradation of the yeast copper transporter, Ctr1p, by the Rsp5 ubiquitin ligase, Traffic, 8, 1375, 10.1111/j.1600-0854.2007.00616.x · DOI
- Madsen, 2007, Copper and iron disorders of the brain, Annu. Rev. Neurosci., 30, 317, 10.1146/annurev.neuro.30.051606.094232 · DOI · Paper page
- Mangala, 2009, Therapeutic targeting of ATP7B in ovarian carcinoma, Clin. Cancer Res., 15, 3770, 10.1158/1078-0432.CCR-08-2306 · DOI
- Mariniello, 2020, Synthetic lethality screening identifies FDA-approved drugs that overcome ATP7B-mediated tolerance of tumor cells to cisplatin, Cancers (Basel), 12, 608, 10.3390/cancers12030608 · DOI
- McMillan, 2017, The emerging role of retromer in neuroprotection, Curr. Opin. Cell Biol., 47, 72, 10.1016/j.ceb.2017.02.004 · DOI · Paper page
- Miyashita, 2003, Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin, Oral Oncol., 39, 157, 10.1016/S1368-8375(02)00038-6 · DOI
- Molloy, 2009, Copper-dependent recycling of hCTR1, the human high affinity copper transporter, J. Biol. Chem., 284, 29704, 10.1074/jbc.M109.000166 · DOI
- Mueller, 2015, The coordinated action of the MVB pathway and autophagy ensures cell survival during starvation, eLife, 4, e07736, 10.7554/eLife.07736 · DOI · Paper page
- Nakayama, 2004, Prognostic value of the Cu-transporting ATPase in ovarian carcinoma patients receiving cisplatin-based chemotherapy, Clin. Cancer Res., 10, 2804, 10.1158/1078-0432.CCR-03-0454 · DOI
- Petris, 1996, Ligand-regulated transport of the Menkes copper P-type ATPase efflux pump from the Golgi apparatus to the plasma membrane: a novel mechanism of regulated trafficking, EMBO J., 15, 6084, 10.1002/j.1460-2075.1996.tb00997.x · DOI
- Petris, 2003, Copper-stimulated endocytosis and degradation of the human copper transporter, hCtr1, J. Biol. Chem., 278, 9639, 10.1074/jbc.M209455200 · DOI
- Phillips-Krawczak, 2015, COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A, Mol. Biol. Cell, 26, 91, 10.1091/mbc.e14-06-1073 · DOI · Paper page
- Polishchuk, 2013, Golgi in copper homeostasis: a view from the membrane trafficking field, Histochem. Cell Biol., 140, 285, 10.1007/s00418-013-1123-8 · DOI
- Polishchuk, 2016, The emerging role of lysosomes in copper homeostasis, Metallomics, 8, 853, 10.1039/C6MT00058D · DOI
- Pufahl, 1997, Metal ion chaperone function of the soluble Cu(I) receptor Atx1, Science, 278, 853, 10.1126/science.278.5339.853 · DOI · Paper page
- Puig, 2002, Biochemical and genetic analyses of yeast and human high affinity copper transporters suggest a conserved mechanism for copper uptake, J. Biol. Chem., 277, 26021, 10.1074/jbc.M202547200 · DOI
- Ren, 2019, X-ray structures of the high-affinity copper transporter Ctr1, Nat. Commun., 10, 1386, 10.1038/s41467-019-09376-7 · DOI
- Safaei, 2005, Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs, Crit. Rev. Oncol. Hematol., 53, 13, 10.1016/j.critrevonc.2004.09.007 · DOI
- Seaman, 2004, Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer, J. Cell Biol., 165, 111, 10.1083/jcb.200312034 · DOI · Paper page
- Seaman, 1998, A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast, J. Cell Biol., 142, 665, 10.1083/jcb.142.3.665 · DOI · Paper page
- Simonetti, 2019, Molecular identification of a BAR domain-containing coat complex for endosomal recycling of transmembrane proteins, Nat. Cell Biol., 21, 1219, 10.1038/s41556-019-0393-3 · DOI · Paper page
- Song, 2004, Role of human copper transporter Ctr1 in the transport of platinum-based antitumor agents in cisplatin-sensitive and cisplatin-resistant cells, Mol. Cancer Ther., 3, 1543, 10.1158/1535-7163.1543.3.12 · DOI
- Steinberg, 2013, A global analysis of SNX27–retromer assembly and cargo specificity reveals a function in glucose and metal ion transport, Nat. Cell Biol., 15, 461, 10.1038/ncb2721 · DOI · Paper page
- Tanner, 1987, Insulin elicits a redistribution of transferrin receptors in 3t3-l1 adipocytes through an increase in the rate-constant for receptor externalization, J. Biol. Chem., 262, 8975, 10.1016/S0021-9258(18)48032-5 · DOI
- Temkin, 2011, SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors, Nat. Cell Biol., 13, 715, 10.1038/ncb2252 · DOI · Paper page
- Tsang, 2020, Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma, Nat. Cell Biol., 22, 412, 10.1038/s41556-020-0481-4 · DOI
- Vanderwerf, 2001, Copper specifically regulates intracellular phosphorylation of the Wilson's disease protein, a human copper-transporting ATPase, J. Biol. Chem., 276, 36289, 10.1074/jbc.M102055200 · DOI
- Voskoboinik, 2003, Protein kinase-dependent phosphorylation of the Menkes copper P-type ATPase, Biochem. Biophys. Res. Commun., 303, 337, 10.1016/S0006-291X(03)00329-2 · DOI
- Wang, 2018, Endosomal receptor trafficking: Retromer and beyond, Traffic, 19, 578, 10.1111/tra.12574 · DOI
- Zhou, 1997, hCTR1: a human gene for copper uptake identified by complementation in yeast, Proc. Natl. Acad. Sci. USA, 94, 7481, 10.1073/pnas.94.14.7481 · DOI
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Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation
Antón-Plágaro, C., Chen, K.-E., Guo, Q., Liu, M., Evans, A. J., Lewis, P. A., Heesom, K. J., Wilkinson, K. A., Collins, B. M., & Cullen, P. J. (2025) · Nature Communications · doi:10.1038/s41467-025-61802-1 · Cited by 14
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Metadata
- Authors
- Curnock, R., & Cullen, P. J.
- Affiliations
- School of Biochemistry , Biomedical Sciences Building , , Bristol BS8 1TD , UK
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2020-08-15
- Volume
- 133
- Issue
- 16
- ISSN
- 1477-9137
- 0021-9533
- PMC
- PMC7473646
- Cited by
- 60
- References
- 3
- Language
- en
- Funders
- Medical Research Council (MR/P018807/1)
- Wellcome Trust (104568/Z/14/Z)
- Lister Institute of Preventive Medicine
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