Distinct function of Chlamydomonas CTRA-CTR transporters in Cu assimilation and intracellular mobilization

Strenkert, Daniela; Schmollinger, Stefan; Paruthiyil, Srinand; Brown, Bonnie C.; Green, Sydnee; Shafer, Catherine M.; Salomé, Patrice; Nelson, Hosea; Blaby-Haas, Crysten E.; Moseley, Jeffrey L.; Merchant, Sabeeha S.

doi:10.1093/mtomcs/mfae013

Title: Distinct function of Chlamydomonas CTRA-CTR transporters in Cu assimilation and intracellular mobilization

Journal Article · Mon Mar 04 00:00:00 EST 2024 · Metallomics (Online)

DOI:https://doi.org/10.1093/mtomcs/mfae013· OSTI ID:2326241

Strenkert, Daniela; Schmollinger, Stefan; Paruthiyil, Srinand; Brown, Bonnie C.; Green, Sydnee; Shafer, Catherine M.; Salomé, Patrice; Nelson, Hosea;

; Moseley, Jeffrey L.; Merchant, Sabeeha S.

Successful acclimation to copper (Cu) deficiency involves a fine balance between Cu import and export. In the green alga Chlamydomonas reinhardtii, Cu import is dependent on a transcription factor, Copper Response Regulator 1 (CRR1), responsible for activating genes in Cu-deficient cells. Among CRR1 target genes are two Cu transporters belonging to the CTR/COPT gene family (CTR1 and CTR2) and a related soluble protein (CTR3). The ancestor of these green algal proteins was likely acquired from an ancient chytrid and contained conserved cysteine-rich domains (named the CTR-associated domains, CTRA) that are predicted to be involved in Cu acquisition. Here, we show by reverse genetics that Chlamydomonas CTR1 and CTR2 are canonical Cu importers albeit with distinct affinities, while loss of CTR3 did not result in an observable phenotype under the conditions tested. Mutation of CTR1, but not CTR2, recapitulates the poor growth of crr1 in Cu-deficient medium, consistent with a dominant role for CTR1 in high-affinity Cu(I) uptake. On the other hand, the overaccumulation of Cu(I) (20 times the quota) in zinc (Zn) deficiency depends on CRR1 and both CTR1 and CTR2. CRR1-dependent activation of CTR gene expression needed for Cu over-accumulation can be bypassed by the provision of excess Cu in the growth medium. Over-accumulated Cu is sequestered into the acidocalcisome but can become remobilized by restoring Zn nutrition. This mobilization is also CRR1-dependent, and requires activation of CTR2 expression, again distinguishing CTR2 from CTR1 and consistent with the lower substrate affinity of CTR2.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2326241

Alternate ID(s):: OSTI ID: 2326167

Journal Information:: Metallomics (Online), Journal Name: Metallomics (Online) Vol. 16 Journal Issue: 3; ISSN 1756-591X

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United Kingdom

Language:: English

References (64)

Metal Preferences and Metallation Foster, Andrew W.; Osman, Deenah; Robinson, Nigel J. Journal of Biological Chemistry, Vol. 289, Issue 41 https://doi.org/10.1074/jbc.R114.588145	journal	August 2014
A C-terminal domain of the membrane copper pump Ctr1 exchanges copper(i) with the copper chaperone Atx1 Xiao, Zhiguang; Wedd, Anthony G. Chemical Communications, Issue 6 https://doi.org/10.1039/b111180a	journal	February 2002
Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): A web tool for generating protein sequence similarity networks Gerlt, John A.; Bouvier, Jason T.; Davidson, Daniel B. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1854, Issue 8 https://doi.org/10.1016/j.bbapap.2015.04.015	journal	August 2015
Copper: An essential metal in biology Festa, Richard A.; Thiele, Dennis J. Current Biology, Vol. 21, Issue 21 https://doi.org/10.1016/j.cub.2011.09.040	journal	November 2011
From economy to luxury: Copper homeostasis in Chlamydomonas and other algae Merchant, Sabeeha S.; Schmollinger, Stefan; Strenkert, Daniela Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1867, Issue 11 https://doi.org/10.1016/j.bbamcr.2020.118822	journal	November 2020
Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain Ohrvik, H.; Nose, Y.; Wood, L. K. Proceedings of the National Academy of Sciences, Vol. 110, Issue 46 https://doi.org/10.1073/pnas.1311749110	journal	October 2013
UniProt: the Universal Protein Knowledgebase in 2023 Nucleic Acids Research, Vol. 51, Issue D1 https://doi.org/10.1093/nar/gkac1052	journal	November 2022
A genome-wide algal mutant library and functional screen identifies genes required for eukaryotic photosynthesis Li, Xiaobo; Patena, Weronika; Fauser, Friedrich Nature Genetics, Vol. 51, Issue 4 https://doi.org/10.1038/s41588-019-0370-6	journal	March 2019
The Proteome of Copper, Iron, Zinc, and Manganese Micronutrient Deficiency in Chlamydomonas reinhardtii Hsieh, Scott I.; Castruita, Madeli; Malasarn, Davin Molecular & Cellular Proteomics, Vol. 12, Issue 1 https://doi.org/10.1074/mcp.M112.021840	journal	October 2012
Drosophila Ctr1A Functions as a Copper Transporter Essential for Development Turski, Michelle L.; Thiele, Dennis J. Journal of Biological Chemistry, Vol. 282, Issue 33 https://doi.org/10.1074/jbc.M703792200	journal	August 2007
Mechanisms for copper acquisition, distribution and regulation Kim, Byung-Eun; Nevitt, Tracy; Thiele, Dennis J. Nature Chemical Biology, Vol. 4, Issue 3 https://doi.org/10.1038/nchembio.72	journal	February 2008
A revised mineral nutrient supplement increases biomass and growth rate in Chlamydomonas reinhardtii: A revised mineral nutrient supplement for Chlamydomonas Kropat, Janette; Hong-Hermesdorf, Anne; Casero, David The Plant Journal, Vol. 66, Issue 5 https://doi.org/10.1111/j.1365-313X.2011.04537.x	journal	March 2011
Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation Letunic, Ivica; Bork, Peer Nucleic Acids Research, Vol. 49, Issue W1 https://doi.org/10.1093/nar/gkab301	journal	April 2021
Interaction between cyanobacterial copper chaperone Atx1 and zinc homeostasis Dainty, Samantha J.; Patterson, Carl J.; Waldron, Kevin J. JBIC Journal of Biological Inorganic Chemistry, Vol. 15, Issue 1 https://doi.org/10.1007/s00775-009-0555-z	journal	June 2009
InterPro in 2022 Paysan-Lafosse, Typhaine; Blum, Matthias; Chuguransky, Sara Nucleic Acids Research, Vol. 51, Issue D1 https://doi.org/10.1093/nar/gkac993	journal	November 2022
FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments Price, Morgan N.; Dehal, Paramvir S.; Arkin, Adam P. PLoS ONE, Vol. 5, Issue 3 https://doi.org/10.1371/journal.pone.0009490	journal	March 2010
Highly accurate protein structure prediction with AlphaFold Jumper, John; Evans, Richard; Pritzel, Alexander Nature https://doi.org/10.1038/s41586-021-03819-2	journal	July 2021
Structural and functional regulation of Chlamydomonas lysosome-related organelles during environmental changes Long, Huan; Fang, Jinhua; Ye, Lian Plant Physiology, Vol. 192, Issue 2 https://doi.org/10.1093/plphys/kiad189	journal	March 2023
Zinc Deficiency Impacts CO ₂ Assimilation and Disrupts Copper Homeostasis in Chlamydomonas reinhardtii Malasarn, Davin; Kropat, Janette; Hsieh, Scott I. Journal of Biological Chemistry, Vol. 288, Issue 15 https://doi.org/10.1074/jbc.M113.455105	journal	February 2013
The Mismetallation of Enzymes during Oxidative Stress Imlay, James A. Journal of Biological Chemistry, Vol. 289, Issue 41 https://doi.org/10.1074/jbc.R114.588814	journal	August 2014
Identification of a copper transporter family in Arabidopsis thaliana Sancenón, Vicente; Puig, Sergi; Mira, Helena Plant Molecular Biology, Vol. 51, Issue 4, p. 577-587 https://doi.org/10.1023/A:1022345507112	journal	January 2003
Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas Hong-Hermesdorf, Anne; Miethke, Marcus; Gallaher, Sean D. Nature Chemical Biology, Vol. 10, Issue 12 https://doi.org/10.1038/nchembio.1662	journal	October 2014
Molecular Characterization of a Putative Arabidopsis thaliana Copper Transporter and Its Yeast Homologue Kampfenkel, Karlheinz; Kushnir, Sergei; Babiychuk, Elena Journal of Biological Chemistry, Vol. 270, Issue 47 https://doi.org/10.1074/jbc.270.47.28479	journal	November 1995
Targeting of Photoreceptor Genes in Chlamydomonas reinhardtii via Zinc-Finger Nucleases and CRISPR/Cas9 Greiner, Andre; Kelterborn, Simon; Evers, Heide The Plant Cell, Vol. 29, Issue 10 https://doi.org/10.1105/tpc.17.00659	journal	October 2017
The Arabidopsis Copper Transporter COPT1 Functions in Root Elongation and Pollen Development Sancenón, Vicente; Puig, Sergi; Mateu-Andrés, Isabel Journal of Biological Chemistry, Vol. 279, Issue 15 https://doi.org/10.1074/jbc.M313321200	journal	January 2004
Membrane sorting in the endocytic and phagocytic pathway of Dictyostelium discoideum Ravanel, Kissia; de Chassey, Benoit; Cornillon, Sophie European Journal of Cell Biology, Vol. 80, Issue 12 https://doi.org/10.1078/0171-9335-00215	journal	December 2001
MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability Katoh, K.; Standley, D. M. Molecular Biology and Evolution, Vol. 30, Issue 4 https://doi.org/10.1093/molbev/mst010	journal	January 2013
Regulated Copper Uptake in Chlamydomonas reinhardtii in Response to Copper Availability Hill, K. L.; Hassett, R.; Kosman, D. Plant Physiology, Vol. 112, Issue 2 https://doi.org/10.1104/pp.112.2.697	journal	October 1996
Expression of the Intracellular COPT3-Mediated Cu Transport Is Temporally Regulated by the TCP16 Transcription Factor Andrés-Colás, Nuria; Carrió-Seguí, Angela; Abdel-Ghany, Salah E. Frontiers in Plant Science, Vol. 9 https://doi.org/10.3389/fpls.2018.00910	journal	July 2018
FEA1 , FEA2 , and FRE1 , Encoding Two Homologous Secreted Proteins and a Candidate Ferrireductase, Are Expressed Coordinately with FOX1 and FTR1 in Iron-Deficient Chlamydomonas reinhardtii Allen, Michael D.; del Campo, José A.; Kropat, Janette Eukaryotic Cell, Vol. 6, Issue 10 https://doi.org/10.1128/EC.00205-07	journal	July 2007
Copper homeostasis in Enterococcus hirae Solioz, Marc; Stoyanov, Jivko V. FEMS Microbiology Reviews, Vol. 27, Issue 2-3 https://doi.org/10.1016/S0168-6445(03)00053-6	journal	June 2003
Gene duplication and neo-functionalization in the evolutionary and functional divergence of the metazoan copper transporters Ctr1 and Ctr2 Logeman, Brandon L.; Wood, L. Kent; Lee, Jaekwon Journal of Biological Chemistry, Vol. 292, Issue 27 https://doi.org/10.1074/jbc.M117.793356	journal	July 2017
Metal ion regulated gene expression: use of a plastocyanin-less mutant of Chlamydomonas reinhardtii to study the Cu(II)-dependent expression of cytochrome c-552. Merchant, S.; Bogorad, L. The EMBO Journal, Vol. 6, Issue 9 https://doi.org/10.1002/j.1460-2075.1987.tb02540.x	journal	September 1987
Efficient targeted DNA editing and replacement in Chlamydomonas reinhardtii using Cpf1 ribonucleoproteins and single-stranded DNA Ferenczi, Aron; Pyott, Douglas Euan; Xipnitou, Andromachi Proceedings of the National Academy of Sciences, Vol. 114, Issue 51 https://doi.org/10.1073/pnas.1710597114	journal	December 2017
Two Chlamydomonas CTR Copper Transporters with a Novel Cys-Met Motif Are Localized to the Plasma Membrane and Function in Copper Assimilation Page, M. Dudley; Kropat, Janette; Hamel, Patrice P. The Plant Cell, Vol. 21, Issue 3 https://doi.org/10.1105/tpc.108.064907	journal	March 2009
The Saccharomyces cerevisiae copper transport protein (Ctr1p). Biochemical characterization, regulation by copper, and physiologic role in copper uptake. Dancis, A.; Haile, D.; Yuan, D. S. Journal of Biological Chemistry, Vol. 269, Issue 41 https://doi.org/10.1016/S0021-9258(18)47300-0	journal	October 1994
hCTR1: A human gene for copper uptake identified by complementation in yeast Zhou, B.; Gitschier, J. Proceedings of the National Academy of Sciences, Vol. 94, Issue 14 https://doi.org/10.1073/pnas.94.14.7481	journal	July 1997
Copper Levels After oral zinc Abdulla, M. The Lancet, Vol. 313, Issue 8116 https://doi.org/10.1016/S0140-6736(79)91051-1	journal	March 1979
Lichens and Their Allies Past and Present Honegger, Rosmarie Plant Relationships, p. 133-183 https://doi.org/10.1007/978-3-031-16503-0_6	book	December 2022
Evidence for Cu(II) Reduction as a Component of Copper Uptake by Saccharomyces cerevisiae Hassett, Richard; Kosman, Daniel J. Journal of Biological Chemistry, Vol. 270, Issue 1 https://doi.org/10.1074/jbc.270.1.128	journal	January 1995
Zn deficiency disrupts Cu and S homeostasis in Chlamydomonas resulting in over accumulation of Cu and Cysteine Strenkert, Daniela; Schmollinger, Stefan; Hu, Yuntao Metallomics, Vol. 15, Issue 7 https://doi.org/10.1093/mtomcs/mfad043	journal	July 2023
Creating the CIPRES Science Gateway for inference of large phylogenetic trees Miller, Mark A.; Pfeiffer, Wayne; Schwartz, Terri 2010 Gateway Computing Environments Workshop (GCE) https://doi.org/10.1109/GCE.2010.5676129	conference	November 2010
A Copper-regulated Transporter Required for Copper Acquisition, Pigmentation, and Specific Stages of Development in Drosophila melanogaster Zhou, Hao; Cadigan, Ken M.; Thiele, Dennis J. Journal of Biological Chemistry, Vol. 278, Issue 48 https://doi.org/10.1074/jbc.M309820200	journal	November 2003
The Arabidopsis COPT6 Transport Protein Functions in Copper Distribution Under Copper-Deficient Conditions Garcia-Molina, Antoni; Andrés-Colás, Nuria; Perea-García, Ana Plant and Cell Physiology, Vol. 54, Issue 8 https://doi.org/10.1093/pcp/pct088	journal	July 2013
Chlamydomonas ATX1 is essential for Cu distribution to multiple cupro‐enzymes and maintenance of biomass in conditions demanding cupro‐enzyme‐dependent metabolic pathways Pham, Keegan L. J.; Schmollinger, Stefan; Merchant, Sabeeha S. Plant Direct, Vol. 6, Issue 2 https://doi.org/10.1002/pld3.383	journal	February 2022
Molecular mechanisms of copper uptake and distribution Puig, Sergi; Thiele, Dennis J. Current Opinion in Chemical Biology, Vol. 6, Issue 2 https://doi.org/10.1016/S1367-5931(02)00298-3	journal	April 2002
COPT6 Is a Plasma Membrane Transporter That Functions in Copper Homeostasis in Arabidopsis and Is a Novel Target of SQUAMOSA Promoter-binding Protein-like 7* Jung, Ha-il; Gayomba, Sheena R.; Rutzke, Michael A. Journal of Biological Chemistry, Vol. 287, Issue 40 https://doi.org/10.1074/jbc.M112.397810	journal	September 2012
Regulation of Copper‐Dependent Endocytosis and Vacuolar Degradation of the Yeast Copper Transporter, Ctr1p, by the Rsp5 Ubiquitin Ligase Liu, Jingxuan; Sitaram, Anand; Burd, Christopher G. Traffic, Vol. 8, Issue 10 https://doi.org/10.1111/j.1600-0854.2007.00616.x	journal	June 2007
Eukaryotic CTR Copper Uptake Transporters Require Two Faces of the Third Transmembrane Domain for Helix Packing, Oligomerization, and Function Aller, Stephen G.; Eng, Edward T.; De Feo, Christopher J. Journal of Biological Chemistry, Vol. 279, Issue 51 https://doi.org/10.1074/jbc.M409421200	journal	September 2004
Regulation of copper transport in Arabidopsis thaliana: a biochemical oscillator? Peñarrubia, Lola; Andrés-Colás, Nuria; Moreno, Joaquín JBIC Journal of Biological Inorganic Chemistry, Vol. 15, Issue 1 https://doi.org/10.1007/s00775-009-0591-8	journal	October 2009
Identification and functional characterization of the ZmCOPT copper transporter family in maize Wang, Hongling; Du, Hanmei; Li, Hongyou PLOS ONE, Vol. 13, Issue 7 https://doi.org/10.1371/journal.pone.0199081	journal	July 2018
The SLC31 (Ctr) copper transporter family Petris, Michael J. Pfl�gers Archiv European Journal of Physiology, Vol. 447, Issue 5 https://doi.org/10.1007/s00424-003-1092-1	journal	February 2004
HMMER web server: interactive sequence similarity searching Finn, R. D.; Clements, J.; Eddy, S. R. Nucleic Acids Research, Vol. 39, Issue suppl https://doi.org/10.1093/nar/gkr367	journal	May 2011
The tonoplast copper transporter COPT5 acts as an exporter and is required for interorgan allocation of copper in Arabidopsis thaliana Klaumann, Sandra; Nickolaus, Sebastian D.; Fürst, Sarah H. New Phytologist, Vol. 192, Issue 2 https://doi.org/10.1111/j.1469-8137.2011.03798.x	journal	June 2011
Systems Biology Approach in Chlamydomonas Reveals Connections between Copper Nutrition and Multiple Metabolic Steps Castruita, Madeli; Casero, David; Karpowicz, Steven J. The Plant Cell, Vol. 23, Issue 4 https://doi.org/10.1105/tpc.111.084400	journal	April 2011
The Yeast Fre1p/Fre2p Cupric Reductases Facilitate Copper Uptake and Are Regulated by the Copper-modulated Mac1p Activator Georgatsou, Elena; Mavrogiannis, Lampros A.; Fragiadakis, George S. Journal of Biological Chemistry, Vol. 272, Issue 21 https://doi.org/10.1074/jbc.272.21.13786	journal	May 1997
The intracellular Arabidopsis COPT5 transport protein is required for photosynthetic electron transport under severe copper deficiency Garcia‐Molina, Antoni; Andrés‐Colás, Nuria; Perea‐García, Ana The Plant Journal, Vol. 65, Issue 6 https://doi.org/10.1111/j.1365-313X.2010.04472.x	journal	February 2011
Copper economy in Chlamydomonas : Prioritized allocation and reallocation of copper to respiration vs. photosynthesis Kropat, Janette; Gallaher, Sean D.; Urzica, Eugen I. Proceedings of the National Academy of Sciences, Vol. 112, Issue 9 https://doi.org/10.1073/pnas.1422492112	journal	February 2015
Copper and zinc metabolism in health and disease: speciation and interactions Bremner, Ian; Beattie, John H. Proceedings of the Nutrition Society, Vol. 54, Issue 2 https://doi.org/10.1079/PNS19950017	journal	July 1995
Deregulated Copper Transport Affects Arabidopsis Development Especially in the Absence of Environmental Cycles Andrés-ColÁs, Nuria; Perea-García, Ana; Puig, Sergi Plant Physiology, Vol. 153, Issue 1 https://doi.org/10.1104/pp.110.153676	journal	March 2010
The CRR1 Nutritional Copper Sensor in Chlamydomonas Contains Two Distinct Metal-Responsive Domains Sommer, Frederik; Kropat, Janette; Malasarn, Davin The Plant Cell, Vol. 22, Issue 12 https://doi.org/10.1105/tpc.110.080069	journal	December 2010
A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis Garcia-Santamarina, Sarela; Probst, Corinna; Festa, Richard A. Nature Chemical Biology, Vol. 16, Issue 3 https://doi.org/10.1038/s41589-019-0437-9	journal	January 2020
Skylign: a tool for creating informative, interactive logos representing sequence alignments and profile hidden Markov models Wheeler, Travis J.; Clements, Jody; Finn, Robert D. BMC Bioinformatics, Vol. 15, Issue 1 https://doi.org/10.1186/1471-2105-15-7	journal	January 2014
A regulator of nutritional copper signaling in Chlamydomonas is an SBP domain protein that recognizes the GTAC core of copper response element Kropat, J.; Tottey, S.; Birkenbihl, R. P. Proceedings of the National Academy of Sciences, Vol. 102, Issue 51 https://doi.org/10.1073/pnas.0507693102	journal	December 2005

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