Diverse Functions and Molecular Properties Emerging for CAX Cation/H⁺ Exchangers in Plants

Abstract

Steep concentration gradients of many ions are actively maintained, with lower concentrations typically located in the cytosol, and higher concentrations in organelles and outside the cell. The vacuole is an important storage organelle for many ions. The concentration gradient of cations is established across the plant tonoplast, in part, by high-capacity cation/H⁺ (CAX) exchange activity. While plants may not be green yeast, analysis of CAX regulation and substrate specificity has been greatly aided by utilizing yeast as an experimental tool. The basic CAX biology in Arabidopsis has immediate relevance toward understanding the functional interplay between diverse transport processes. The long-range applied goals are to identify novel transporters and express them in crop plants in order to “mine” nutrients out of the soil and into plants. In doing so, this could boost the levels of essential nutrients in plants.

Key words

Autoinhibition - phytoremediation - nutrition - CAX - cation specificity - Ca²⁺/H⁺ exchanger

References

• 1 Allen G. J., Kwak J. M., Chu S. P., Llopis J., Tsien R. Y., Harper J. F., Schroeder J. I.. Cameleon calcium indicator reports cytoplasmic calcium dynamics in Arabidopsis guard cells.  The Plant Journal. (1999);  19 735-747
• 2 Alonso J. M., Stepanova A. N., Leisse T. J., Kim C. J., Chen H., Shinn P., Stevenson D. K., Zimmerman J., Barajas P., Cheuk R., Gadrinab C., Heller C., Jeske A., Koesema E., Meyers C. C., Parker H., Prednis L., Ansari Y., Choy N., Deen H., Geralt M., Hazari N., Hom E., Karnes M., Mulholland C., Ndubaku R., Schmidt I., Guzman P., Aguilar-Henonin L., Schmid M., Weigel D., Carter D. E., Marchand T., Risseeuw E., Brogden D., Zeko A., Crosby W. L., Berry C. C., Ecker J. R.. Genome-wide insertional mutagenesis of Arabidopsis thaliana.  Science. (2003);  301 653-657
• 3 The Arabidopsis Genome Initiative . Analysis of the genome sequence of the flowering plant Arabidopsis thaliana.  Nature. (2000);  408 796-815
• 4 Bernstein L., Shear C. B., LaHaye P. A., Epstein E.. Calcium and salt tolerance of plants.  Science. (1970);  167 1387-1388
• 5 Bradshaw H. D.. Mutations in CAX1 produce phenotypes characteristic of plants tolerant to serpentine soils.  New Phytologist. (2005);  167 81-88
• 6 Bryant R. J., Cadogan J., Weaver C. M.. The new dietary reference intakes for calcium: implications for osteoporosis.  Journal of the American College of Nutrition. (1999);  18 406S-412S
• 7 Cai X., Lytton J.. The cation/Ca²⁺ exchanger superfamily: phylogenetic analysis and structural implications.  Molecular Biology and Evolution. (2004);  21 1692-1703
• 8 Catalá R., Santos E., Alonso J. M., Ecker J. R., Martinez-Zapater J. M., Salinas J.. Mutations in the Ca²⁺/H⁺ transporter CAX1 increase CBF/DREB1 expression and the cold-acclimation response in Arabidopsis. .  Plant Cell. (2003);  15 2940-2951
• 9 Cheng N.-H., Hirschi K. D.. Cloning and characterization of CXIP1, a novel PICOT domain-containing Arabidopsis protein that associates with CAX1.  Journal of Biological Chemistry. (2003);  278 6503-6509
• 10 Cheng N.-H., Liu J.-Z., Nelson R. S., Hirschi K. D.. Characterization of CXIP4, a novel Arabidopsis protein that activates the H⁺/Ca²⁺ antiporter, CAX1.  FEBS Letters. (2004 a);  559 99-106
• 11 Cheng N.-H., Pittman J. K., Barkla B. J., Shigaki T., Hirschi K. D.. The Arabidopsis cax1 mutant exhibits impaired ion homeostasis, development, and hormonal responses and reveals interplay among vacuolar transporters.  Plant Cell. (2003);  15 347-364
• 13 Cheng N.-H., Pittman J. K., Shigaki T., Lachmansingh J., LeClere S., Lahner B., Salt D. E., Hirschi K. D.. Functional association of Arabidopsis CAX1 and CAX3 is required for normal growth and ion homeostasis.  Plant Physiology. (2005);  138 2048-2060
• 14 Cheng N.-H., Pittman J. K., Zhu J.-K., Hirschi K. D.. The protein kinase SOS2 activates the Arabidopsis H⁺/Ca²⁺ antiporter CAX1 to integrate calcium transport and salt tolerance.  Journal of Biological Chemistry. (2004 b);  279 2922-2926
• 15 Cunningham K. W., Fink G. R.. Calcineurin inhibits VCX1-dependent H⁺/Ca²⁺ exchange and induces Ca²⁺-ATPases in Saccharomyces cerevisiae.  Molecular and Cellular Biology. (1996);  16 2226-2237
• 12 del Pozo L., Osaba L., Corchero J., Jimenez A.. A single nucleotide change in the MNR1 (VCX1/HUM1) gene determines resistance to manganese in Saccharomyces cerevisiae. .  Yeast. (1999);  15 371-375
• 16 Denis V., Cyert M. S.. Internal Ca²⁺ release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue.  Journal of Cell Biology. (2002);  156 29-34
• 17 Ettinger W. F., Clear A. M., Fanning K. J., Peck M. L.. Identification of a Ca²⁺/H⁺ antiport in the plant chloroplast thylakoid membrane.  Plant Physiology. (1999);  119 1379-1385
• 18 Felsenstein J.. PHYLIP - Phylogeny Inference Package (version 3.2).  Cladistics. (1989);  5 164-166
• 19 Förster C., Kane P. M.. Cytosolic Ca²⁺ homeostasis is a constitutive function of the V-ATPase in Saccharomyces cerevisiae.  Journal of Biological Chemistry. (2000);  275 38245-38253
• 20 Fox T. C., Guerinot M. L.. Molecular biology of cation transport in plants.  Annual Review of Plant Physiology and Plant Molecular Biology. (1998);  49 669-696
• 22 Harper J. F., Hong B., Hwang I., Guo H. Q., Stoddard R., Huang J. F., Palmgren M. G., Sze H.. A novel calmodulin-regulated Ca²⁺-ATPase (ACA2) from Arabidopsis with an N-terminal autoinhibitory domain.  Journal of Biological Chemistry. (1998);  273 1099-1106
• 23 Hirschi K. D.. Expression of Arabidopsis CAX1 in tobacco: altered calcium homeostasis and increased stress sensitivity.  Plant Cell. (1999);  11 2113-2122
• 25 Hirschi K. D.. The calcium conundrum. Both versatile nutrient and specific signal.  Plant Physiology. (2004);  136 2438-2442
• 26 Hirschi K. D., Korenkov V. D., Wilganowski N. L., Wagner G. J.. Expression of Arabidopsis CAX2 in tobacco: altered metal accumulation and increased manganese tolerance.  Plant Physiology. (2000);  124 125-133
• 27 Hirschi K. D., Miranda M. L., Wilganowski N. L.. Phenotypic changes in Arabidopsis caused by expression of a yeast vacuolar Ca²⁺/H⁺ antiporter.  Plant Molecular Biology. (2001);  46 57-65
• 28 Hirschi K., Zhen R., Cunningham K. W., Rea P. A., Fink G. R.. CAX1, a H⁺/Ca²⁺ antiporter from Arabidopsis.  Proceedings of the National Academy of Sciences of the USA. (1996);  93 8782-8786
• 30 Ivey D. M., Guffanti A. A., Zemsky J., Pinner E., Karpel R., Padan E., Schuldiner S., Krulwich T. A.. Cloning and characterization of a putative Ca²⁺/H⁺ antiporter gene from Escherichia coli upon functional complementation of Na⁺/H⁺ antiporter-deficient strains by the overexpressed gene.  Journal of Biological Chemistry. (1993);  268 11296-11303
• 31 Kamiya T., Maeshima M.. Residues in internal repeats of the rice cation/H⁺ exchanger are involved in the transport and selection of cations.  Journal of Biological Chemistry. (2004);  279 812-819
• 32 Kamiya T., Akahori T., Maeshima M.. Expression profile of the genes for rice cation/H⁺ exchanger family and functional analysis in yeast.  Plant and Cell Physiology. (2005);  46 1735-1740
• 33 Kasai N., Muto S.. Ca²⁺ pump and Ca²⁺/H⁺ antiporter in plasma membrane vesicles isolated by aqueous two-phase partitioning from maize leaves.  Journal of Membrane Biology. (1990);  114 133-142
• 34 Kruckeberg A. R.. The ecology of serpentine soils: a symposium. III. Plant species in relation to serpentine soils.  Ecology. (1954);  35 267-274
• 36 Kyte J., Doolittle R. F.. A simple method for displaying the hydropathic character of a protein.  Journal of Molecular Biology. (1982);  157 105-132
• 37 LaHaye P. A., Epstein E.. Salt toleration by plants: enhancement with calcium.  Science. (1969);  166 395-396
• 38 Locke E. G., Bonilla M., Liang L., Takita Y., Cunningham K. W.. A homolog of voltage-gated Ca²⁺ channels stimulated by depletion of secretory Ca²⁺ in yeast.  Molecular and Cellular Biology. (2000);  20 6686-6694
• 39 MacDiarmid C. W., Milanick M. A., Eide D. J.. Biochemical properties of vacuolar zinc transport systems of Saccharomyces cerevisiae.  Journal of Biological Chemistry. (2002);  277 39187-39194
• 40 Maeshima M.. Tonoplast transporters: organization and function.  Annual Review of Plant Physiology and Plant Molecular Biology. (2001);  52 469-497
• 41 Marchi V., Sorin A., Wei Y., Rao R.. Induction of vacuolar Ca²⁺-ATPase and H⁺/Ca²⁺ exchange activity in yeast mutants lacking Pmr1, the Golgi Ca²⁺-ATPase.  FEBS Letters. (1999);  9 181-186
• 42 Marshner H.. Mineral Nutrition of Higher Plants. 2nd ed. London; Academic Press (1995)
• 43 Mäser P., Thomine S., Schroeder J. I., Ward J. M., Hirschi K., Sze H., Talke I. N., Amtmann A., Maathuis F. J. M., Sanders D., Harper J. F., Tchieu J., Gribskov M., Persans M. W., Salt D. E., Kim S. A., Guerinot M. L.. Phylogenetic relationships within cation transporter families of Arabidopsis. .  Plant Physiology. (2001);  126 1646-1667
• 44 Miseta A., Kellermayer R., Aiello D. P., Fu L., Bedwell D. M.. The vacuolar Ca²⁺/H⁺ exchanger Vcx1p/Hum1p tightly controls cystolic Ca²⁺ levels in S. cerevisiae. .  FEBS Letters. (1999);  451 132-136
• 49 Page R. D.. TreeView: an application to display phylogenetic trees on personal computers.  Computer Applications in the Biosciences. (1996);  12 357-358
• 45 Park S., Cheng N. H., Pittman J. K., Yoo K. S., Park J., Smith R. H., Hirschi K. D.. Increased calcium levels and prolonged shelf life in tomatoes expressing Arabidopsis H⁺/Ca²⁺ transporters.  Plant Physiology. (2005 a);  139 1194-1206
• 46 Park S., Kang T.-S., Kim C.-K., Han J.-S., Kim S., Smith R. H., Pike L. M., Hirschi K. D.. Genetic manipulation for enhancing calcium content in potato tuber.  Journal of Agrucultural and Food Chemistry. (2005 b);  53 5598-5603
• 47 Park S., Kim C.-K., Pike L. M., Smith R. H., Hirschi K. D.. Increased calcium in carrots by expression of an Arabidopsis H⁺/Ca²⁺ transporter.  Molecular Breeding. (2004);  14 275-282
• 48 Pittman J. K., Cheng N.-H., Shigaki T., Kunta M., Hirschi K. D.. Functional dependence on calcineurin by variants of the Saccharomyces cerevisiae vacuolar Ca²⁺/H⁺ exchanger Vcx1p.  Molecular Microbiology. (2004 a);  54 1104-1116
• 50 Pittman J. K., Hirschi K. D.. Don't shoot the (second) messenger: endomembrane transporters and binding proteins modulate cytosolic Ca²⁺ levels.  Current Opinion in Plant Biology. (2003);  6 257-262
• 51 Pittman J. K., Shigaki T., Cheng N.-H., Hirschi K. D.. Mechanism of N-terminal autoinhibition in the Arabidopsis Ca²⁺/H⁺ antiporter CAX1.  Journal of Biological Chemistry. (2002 a);  277 26452-26459
• 52 Pittman J. K., Shigaki T., Hirschi K. D.. Evidence of differential pH regulation of the Arabidopsis vacuolar Ca²⁺/H⁺ antiporters CAX1 and CAX2.  FEBS Letters. (2005);  579 2648-2656
• 53 Pittman J. K., Shigaki T., Marshall J. L., Morris J. L., Cheng N.-H., Hirschi K. D.. Functional and regulatory analysis of the Arabidopsis thaliana CAX2 cation transporter.  Plant Molecular Biology. (2004 b);  56 959-971
• 54 Pittman J. K., Sreevidya C. S., Shigaki T., Ueoka-Nakanishi H., Hirschi K. D.. Distinct N-terminal regulatory domains of Ca²⁺/H⁺ antiporters.  Plant Physiology. (2002 b);  130 1054-1062
• 55 Schaaf G., Catoni E., Fitz M., Schwacke R., Schneider A., von Wirén N., Frommer W. B.. A putative role for the vacuolar calcium/manganese proton antiporter AtCAX2 in heavy metal detoxification.  Plant Biology. (2002);  4 612-618
• 56 Schumaker K. S., Sze H.. Calcium transport into the vacuole of oat roots. Characterization of H⁺/Ca²⁺ exchange activity.  Journal of Biological Chemistry. (1986);  261 12172-12178
• 57 Senes A., Gerstein M., Engelman D. M.. Statistical analysis of amino acid patterns in transmembrane helices: the GXXXG motif occurs frequently and in association with beta-branched residues at neighboring positions.  Journal of Molecular Biology. (2000);  296 921-936
• 58 Shaul O., Hilgemann D. W., de-Almeida-Engler J., Van Montagu M. V., Inze D., Galili G.. Cloning and characterization of a novel Mg²⁺/H⁺ exchanger.  EMBO Journal. (1999);  18 3973-3980
• 59 Shigaki T., Barkla B. J., Miranda-Vergara M. C., Zhao J., Pantoja O., Hirschi K. D.. Identification of a crucial histidine involved in metal transport activity in the Arabidopsis cation/H⁺ exchanger CAX1.  Journal of Biological Chemistry. (2005);  280 30136-30142
• 60 Shigaki T., Cheng N.-H., Pittman J. K., Hirschi K.. Structural determinants of Ca²⁺ transport in the Arabidopsis H⁺/Ca²⁺ antiporter CAX1.  Journal of Biological Chemistry. (2001);  276 43152-43159
• 61 Shigaki T., Hirschi K.. Characterization of CAX-like genes in plants: implications for functional diversity.  Gene. (2000);  257 291-298
• 62 Shigaki T., Pittman J. K., Hirschi K. D.. Manganese specificity determinants in the Arabidopsis metal/H⁺ antiporter CAX2.  Journal of Biological Chemistry. (2003);  278 6610-6617
• 63 Shigaki T., Sreevidya C., Hirschi K. D.. Analysis of the Ca²⁺ domain in the Arabidopsis H⁺/Ca²⁺ antiporters CAX1 and CAX3.  Plant Molecular Biology. (2002);  50 475-483
• 65 Sonnhammer E. L. L., von Heijne G., Krogh A.. A hidden Markov model for predicting transmembrane helices in protein sequences.  Proceedings of ISMB. (1998);  6 175-182
• 66 Sze H., Li X., Palmgren M.. Energization of the plant cell membranes by H⁺-pumping ATPases: biosynthesis and regulation.  Plant Cell. (1999);  11 677-689
• 67 Sze H., Liang F., Hwang I., Curran A. C., Harper J. F.. Diversity and regulation of plant Ca²⁺ pumps: insights from expression in yeast.  Annual Review of Plant Physiology and Plant Molecular Biology. (2000);  51 433-462
• 68 Thompson J. D., Higgins D. G., Gibson T. J.. CLUSTAK W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice.  Nucleic Acids Research. (1994);  22 4673-4680
• 69 Tucker G.. Nutritional enhancement of plants.  Current Opinion in Biotechnology. (2003);  14 221-225
• 70 Ueoka-Nakanishi H., Maeshima M.. Quantification of Ca²⁺/H⁺ antiporter VCAX1p in vacuolar membranes and its absence in roots of mung bean.  Plant and Cell Physiology. (2000);  41 1067-1071
• 71 Ueoka-Nakanishi H., Nakanishi Y., Tanaka Y., Maeshima M.. Properties and molecular cloning of Ca²⁺/H⁺ antiporter in the vacuolar membrane of mung bean.  European Journal of Biochemistry. (1999);  262 417-425
• 73 Wiebe C. A., DiBattista E. R., Fliegel L.. Functional role of polar amino acid residues in Na⁺/H⁺ exchangers.  Biochemical Journal. (2001);  357 1-10
• 74 Yang X., Feng Y., He Z., Stoffella P. J.. Molecular mechanisms of heavy metal hyperaccumulation and phytoremediation.  Journal of Trace Elements in Medicine and Biology. (2005);  18 339-353
• 75 Zhang H.-X., Blumwald E.. Transgenic salt-tolerant tomato plants accumulate salt in foliage but not in fruit.  Nature Biotechnology. (2001);  19 765-768
• 76 Zhang H.-X., Hodson J. N., Williams J. P., Blumwald E.. Engineering salt-tolerant Brassica plants: characterization of yield and seed oil quality in transgenic plants with increased vacuolar sodium accumulation.  Proceedings of the National Academy of Sciences of the USA. (2001);  98 12832-12836
• 77 Zhu J.-K.. Cell signaling under salt, water and cold stresses.  Current Opinion in Plant Biology. (2001);  4 401-406

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