AtHMA3, a plant P<sub>1B</sub>‐ATPase, functions as a Cd/Pb transporter in yeast

Gravot, Antoine; Lieutaud, Aurélie; Verret, Frédéric; Auroy, Pascaline; Vavasseur, Alain; Richaud, Pierre

doi:10.1016/s0014-5793(04)00072-9

Cited by 168 publications

(136 citation statements)

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“…The key physiological roles of plant Zn 2ϩ -ATPases (10,11,41,54,55) likely requires fine regulation of their turnover, location, and interaction with other proteins. Analysis of their sequences reveals the presence of interesting C and N termini that might play regulatory roles as it is the case of N-MBDs in Cu ϩ -ATPases (15,27,32,33,56).…”

Section: Discussionmentioning

confidence: 99%

A Novel Regulatory Metal Binding Domain Is Present in the C Terminus of Arabidopsis Zn2+-ATPase HMA2

Eren

Kennedy

Maroney

et al. 2006

Journal of Biological Chemistry

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HMA2 is a Zn2؉ -ATPase from Arabidopsis thaliana. It contributes to the maintenance of metal homeostasis in cells by driving Zn 2؉ efflux. Distinct from P 1B -type ATPases, plant Zn 2؉ -ATPases have long C-terminal sequences rich in Cys and His. Removal of the 244 amino acid C terminus of HMA2 leads to a 43% reduction in enzyme turnover without significant effect on the Zn 2؉ K1 ⁄ 2 for enzyme activation. Characterization of the isolated HMA2 C terminus showed that this fragment binds three Zn 2؉ with high affinity (K d ‫؍‬ 16 ؎ 3 nM). Circular dichroism spectral analysis indicated the presence of 8% ␣-helix, 45% ␤-sheet, and 48% random coil in the C-terminal peptide with noticeable structural changes upon metal binding (8% ␣-helix, 39% ␤-sheet, and 52% random coil , Cd 2ϩ , Pb 2ϩ , Co 2ϩ ) across biological membranes (1-3). These enzymes play critical roles in maintaining heavy metal homeostasis in organisms ranging from bacteria to humans (4 -8). Plant genomes appear to contain multiple (eight or nine) genes encoding P 1B -ATPases with various metal selectivities (Zn 2ϩ -ATPases, Cu ϩ -ATPases, and others with metal dependence is still to be determined) (3,8,9). Distinctly, only two Cu ϩ -ATPase isoforms are found in other eukaryotes (1-3). We recently characterized the functional role of Arabidopsis thaliana HMA2 (10). This Zn 2ϩ -ATPase drives the efflux of metals out of the cell and is activated by Zn 2ϩ and Cd 2ϩ with quite low apparent affinities (0.1-0.2 M). Analysis of A. thaliana hma2 knock-out mutants revealed a significant increase in whole plant Zn 2ϩ and Cd 2ϩ levels (10). This observation along with the plasma membrane localization and strong expression in the plant vasculature suggests that HMA2 is responsible for Zn 2ϩ uploading into the phloem (10, 11). P 1B -type ATPases have 6 -8 transmembrane fragments responsible for metal translocation and a large cytoplasmic loop involved in ATP binding and hydrolysis (1-3). Conserved residues in transmembrane fragments H6, H7, and H8 participate in metal coordination during transport and provide signature sequences that predict the metal selectivity of P 1B -type ATPases (3, 12). Most of these enzymes also have highly conserved N-terminal metal binding domains (N-MBDs) 2 characterized by the CXXC sequences (3, 6, 7, 13). These Cys residues are responsible for metal coordination, and can bind both monovalent and divalent cations (Cu ϩ , Cu 2ϩ , Zn 2ϩ , Cd 2ϩ ) (14 -19). In Cu ϩ -ATPases, N-MBDs receive the metal from specific Cu ϩ -chaperones (20 -26). Removal of the N-MBDs metal binding capability by truncation or mutation leads to reduced enzyme activity with small or no changes in metal affinity (27-33). Lutsenko and co-workers (34) have shown the Cu ϩ -dependent interaction of Wilson's disease protein N-MBDs with the large ATP binding cytoplasmic loop. In our laboratory, we have observed that N-MBDs of Archaeoglobus fulgidus CopA, a Cu ϩ -ATPase, and CopB, a Cu 2ϩ -ATPase with a His-rich N-MBD, control the turnover rate of these enzymes but do not aff...

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Section: Discussionmentioning

confidence: 99%

A Novel Regulatory Metal Binding Domain Is Present in the C Terminus of Arabidopsis Zn2+-ATPase HMA2

Eren

Kennedy

Maroney

et al. 2006

Journal of Biological Chemistry

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“…After 2 weeks, the young plantlets were placed on sand for an additional 3-week period in a controlled environment (8 h of light with 300 mE s 21 light intensity, 22°C, 70% relative humidity). Plants of similar rosette diameters were then transferred to a hydroponic culture using the nutritive solution described by Gravot et al (2004) for an acclimation of 3 d. L-NAME and CdCl 2 treatments were started at 1 and 2 h, respectively, after the start of illumination.…”

Section: Plant Materials and Growth Conditionsmentioning

confidence: 99%

Nitric Oxide Contributes to Cadmium Toxicity in Arabidopsis by Promoting Cadmium Accumulation in Roots and by Up-Regulating Genes Related to Iron Uptake

et al. 2009

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Nitric oxide (NO) functions as a cell-signaling molecule in plants. In particular, a role for NO in the regulation of iron homeostasis and in the plant response to toxic metals has been proposed. Here, we investigated the synthesis and the role of NO in plants exposed to cadmium (Cd 2+ ), a nonessential and toxic metal. We demonstrate that Cd 2+ induces NO synthesis in roots and leaves of Arabidopsis (Arabidopsis thaliana) seedlings. This production, which is sensitive to NO synthase inhibitors, does not involve nitrate reductase and AtNOA1 but requires IRT1, encoding a major plasma membrane transporter for iron but also Cd 2+ . By analyzing the incidence of NO scavenging or inhibition of its synthesis during Cd 2+ treatment, we demonstrated that NO contributes to Cd 2+ -triggered inhibition of root growth. To understand the mechanisms underlying this process, a microarray analysis was performed in order to identify NO-modulated root genes up-and down-regulated during Cd 2+ treatment. Forty-three genes were identified encoding proteins related to iron homeostasis, proteolysis, nitrogen assimilation/metabolism, and root growth. These genes include IRT1. Investigation of the metal and ion contents in Cd 2+ -treated roots in which NO synthesis was impaired indicates that IRT1 up-regulation by NO was consistently correlated to NO's ability to promote Cd 2+ accumulation in roots. This analysis also highlights that NO is responsible for Cd 2+ -induced inhibition of root Ca 2+ accumulation. Taken together, our results suggest that NO contributes to Cd 2+ toxicity by favoring Cd 2+ versus Ca 2+ uptake and by initiating a cellular pathway resembling those activated upon iron deprivation.

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“…EcZntA and SaCadA are involved in zinc or cadmium excretion and tolerance in Escherichia coli and Staphylococcus aureus, respectively (Nies, 2003). AtHMA2 and AtHMA4 probably play a role in zinc translocation in the plant (Mills et al, 2003;Hussain et al, 2004), while functional studies in yeast suggest that AtHMA3 is a cadmium/lead transporter (Gravot et al, 2004). In addition, AhHMA3 and TcHMA4 are constitutively highly expressed in the zinc hyperaccumulator A. halleri and the zinc/ cadmium hyperaccumulator T. caerulescens, respectively, when compared to Arabidopsis.…”

Section: The Copt Familymentioning

confidence: 99%

A Comparative Inventory of Metal Transporters in the Green Alga Chlamydomonas reinhardtii and the Red Alga Cyanidioschizon merolae

et al. 2005

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As in all organisms, metal cations are crucial for nutrition in plants. Several metals, such as copper, iron, zinc, and manganese, act as important cofactors for many enzymes and are essential for both mitochondrial and chloroplast functions. However, when supplied in excess, these essential cations can become toxic, like heavy metals with no generally established function, such as cadmium, lead, or mercury. To maintain micronutrient metal homeostasis and to cope with the deleterious effects of nonessential heavy metals, plants have developed a complex network of metal uptake, chelation, trafficking, and storage processes. Metal transporters are required to maintain metal homeostasis and thus constitute important components of this network (Clemens, 2001;Hall and Williams, 2003).In recent years, a number of membrane transport protein families have been implicated in metal homeostasis in plants. These include the cation diffusion facilitators (CDF), the Zrt-, Irt-like proteins (ZIP), the cation exchangers (CAX), the copper transporters (COPT), the heavy-metal P-type ATPases (HMA), the natural resistance-associated macrophage proteins (NRAMP), and the ATP-binding cassette (ABC) transporters (Williams et al., 2000;Maser et al., 2001;Cobbett et al., 2003;Hall and Williams, 2003). These transporters are encoded by multigene families. For example, 15 ZIP genes, 12 metal tolerance protein (MTP) genes, and 8 HMA genes are present in the Arabidopsis (Arabidopsis thaliana) genome (Cobbett et al., 2003;Delhaize et al., 2003). However, the transport specificities, patterns of expression, or subcellular localizations of metal transport proteins are still largely unknown. To further understand plant metal homeostasis, it will be necessary to elucidate the contribution of each of these transporters to the uptake, trafficking, and storage of essential metals, as well as to the detoxification of toxic heavy metals.In this article, we present an overview of our current knowledge of the metal transport function in metal homeostasis and tolerance in eukaryotes, with a special emphasis on plants. We also provide a timely inventory of putative metal transporters in two unicellular algal models, the green alga Chlamydomonas reinhardtii and the red alga Cyanidioschizon merolae. These new data should facilitate functional genomics and molecular analysis of metal homeostasis and tolerance in photosynthetic organisms. Moreover, the comparison of metal transporters from species belonging to the red and green algae with those of the land plant Arabidopsis, as well as with their human and yeast homologs, allows some light to be shed on the molecular evolution of metal homeostasis and tolerance systems. TWO UNICELLULAR ALGAL MODEL SYSTEMS

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AtHMA3, a plant P_1B‐ATPase, functions as a Cd/Pb transporter in yeast

Cited by 168 publications

References 30 publications

A Novel Regulatory Metal Binding Domain Is Present in the C Terminus of Arabidopsis Zn2+-ATPase HMA2

A Novel Regulatory Metal Binding Domain Is Present in the C Terminus of Arabidopsis Zn2+-ATPase HMA2

Nitric Oxide Contributes to Cadmium Toxicity in Arabidopsis by Promoting Cadmium Accumulation in Roots and by Up-Regulating Genes Related to Iron Uptake

A Comparative Inventory of Metal Transporters in the Green Alga Chlamydomonas reinhardtii and the Red Alga Cyanidioschizon merolae

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AtHMA3, a plant P1B‐ATPase, functions as a Cd/Pb transporter in yeast

Cited by 168 publications

References 30 publications

A Novel Regulatory Metal Binding Domain Is Present in the C Terminus of Arabidopsis Zn2+-ATPase HMA2

A Novel Regulatory Metal Binding Domain Is Present in the C Terminus of Arabidopsis Zn2+-ATPase HMA2

Nitric Oxide Contributes to Cadmium Toxicity in Arabidopsis by Promoting Cadmium Accumulation in Roots and by Up-Regulating Genes Related to Iron Uptake

A Comparative Inventory of Metal Transporters in the Green Alga Chlamydomonas reinhardtii and the Red Alga Cyanidioschizon merolae

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AtHMA3, a plant P_1B‐ATPase, functions as a Cd/Pb transporter in yeast