The multi-layered regulation of copper translocating P-type ATPases

Veldhuis, Nicholas A.; Gaeth, Ann P.; Pearson, Richard B.; Gabriel, Kipros; Camakaris, James

doi:10.1007/s10534-008-9183-2

Cited by 63 publications

(58 citation statements)

References 128 publications

(159 reference statements)

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“…Other Cu-ATPases can function in either uptake or efflux, and with Cu + and/or Cu 2+ as the primary transported metal ion(s), although some catalyze transport of other monovalent and divalent heavy metal (HM) cations as well [Odermatt et al, 1993;Solioz and Stoyanov, 2003]. Their functions, regulation and biogenesis have been studied extensively [Lutsenko et al, 2007;Veldhuis et al, 2009].…”

Section: +mentioning

confidence: 99%

The P-Type ATPase Superfamily

Chan

Babayan²,

Blyumin³

et al. 2010

Microb Physiol

100

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P-type ATPases function to provide homeostasis in higher eukaryotes, but they are essentially ubiquitous, being found in all domains of life. Thever and Saier [J Memb Biol 2009;229:115–130] recently reported analyses of eukaryotic P-type ATPases, dividing them into nine functionally characterized and 13 functionally uncharacterized (FUPA) families. In this report, we analyze P-type ATPases in all major prokaryotic phyla for which complete genome sequence data are available, and we compare the results with those for eukaryotic P-type ATPases. Topological type I (heavy metal) P-type ATPases predominate in prokaryotes (approx. tenfold) while type II ATPases (specific for Na⁺,K⁺, H⁺ Ca²⁺, Mg²⁺ and phospholipids) predominate in eukaryotes (approx. twofold). Many P-type ATPase families are found exclusively in prokaryotes (e.g. Kdp-type K⁺ uptake ATPases (type III) and all ten prokaryotic FUPA familes), while others are restricted to eukaryotes (e.g. phospholipid flippases and all 13 eukaryotic FUPA families). Horizontal gene transfer has occurred frequently among bacteria and archaea, which have similar distributions of these enzymes, but rarely between most eukaryotic kingdoms, and even more rarely between eukaryotes and prokaryotes. In some bacterial phyla (e.g. Bacteroidetes, Flavobacteria and Fusobacteria), ATPase gene gain and loss as well as horizontal transfer occurred seldom in contrast to most other bacterial phyla. Some families (i.e. Kdp-type ATPases) underwent far less horizontal gene transfer than other prokaryotic families, possibly due to their multisubunit characteristics. Functional motifs are better conserved across family lines than across organismal lines, and these motifs can be family specific, facilitating functional predictions. In some cases, gene fusion events created P-type ATPases covalently linked to regulatory catalytic enzymes. In one family (FUPA Family 24), a type I ATPase gene (N-terminal) is fused to a type II ATPase gene (C-terminal) with retention of function only for the latter. Several pseudogene-encoded nonfunctional ATPases were identified. Genome minimalization led to preferential loss of P-type ATPase genes. We suggest that in prokaryotes and some unicellular eukaryotes, the primary function of P-type ATPases is protection from extreme environmental stress conditions. The classification of P-type ATPases of unknown function into phylogenetic families provides guides for future molecular biological studies.

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Section: +mentioning

confidence: 99%

The P-Type ATPase Superfamily

Chan

Babayan²,

Blyumin³

et al. 2010

Microb Physiol

100

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“…Only a small fraction of the total Cu-ATPases is found at the plasma membrane (44), likely due to rapid endocytosis (45). Recent studies indicate that the trafficking of Cu-ATPase could also be coupled to hormone-mediated signaling, changes in Ca 2ϩ fluxes, and kinasemediated phosphorylation (46). These data provide the first mechanistic evidence of the tight link between copper homeostasis and such complex physiological responses as lactation (41), neuronal activity (47), hypoxia (48), and others.…”

Section: Regulation Of Copper Transport Via Traffickingmentioning

confidence: 99%

Copper Transport in Mammalian Cells: Special Care for a Metal with Special Needs

Kaplan

Lutsenko

2009

Journal of Biological Chemistry

143

115

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Copper plays an essential role in human physiology. It is required for respiration, radical defense, neuronal myelination, angiogenesis, and many other processes. Copper has distinct physicochemical properties that pose uncommon challenges for its transport across biological membranes. Only small amounts of copper are present in biological fluids, and essentially none of it exists in a free ion form. These properties and the low redox potential of copper dictate special structural and mechanistic features in copper transporters. This minireview discusses molecular mechanisms through which copper enters and exits human cells. Dietary Acquisition and Excretion of CopperDietary copper is acquired via the small intestine through a process that is not fully understood. Earlier studies showing the major involvement of the mammalian transporter CTR1 in cellular copper uptake (1) led to the assumption that in enterocytes CTR1 mediates the acquisition of dietary copper at the apical membrane. Recent studies questioned this assumption. Cell-surface labeling revealed that the majority (and perhaps all) of surface hCTR1 3 in Caco-2 cells, a model for enterocytes, is located at the basolateral border, i.e. the blood side, and thus cannot mediate apical copper entry (2). Basolateral CTR1 is also observed in renal cells and hepatocytes. Furthermore, in mice with an intestine-specific deletion of CTR1, enterocyte copper levels are higher (and not lower) than in normal mice, arguing against the direct role of CTR1 in apical uptake (3). It seems most likely that in enterocytes some other transporter plays a major role in copper uptake from the fluid that exits the stomach (Fig. 1). The existence of such pathways is supported by the observation that fibroblasts from CTR1 knock-out mice retain ϳ25-30% of their copper uptake (4). Divalent metal transporter DMT1 was suggested as a candidate for copper uptake (5). Other systems not thought of as major copper transporters may accept copper as a surrogate substrate and contribute to the overall copper absorption. Endocytic mechanisms may also contribute to apical copper entry. It is not yet clear how the copper pool from apical dietary uptake in enterocytes interacts with the copper that enters from the blood (Fig. 1).In intestinal cells and tissue, CTR1 was detected at the plasma membrane and in vesicles (2, 6). Thus, CTR1 in enterocytes may take up copper from the blood (as in other cell types) and also from the vesicles in which dietary copper has been sequestered (Fig. 1). This latter role is suggested by the finding that, although the intestinal deletion of CTR1 results in high copper levels in enterocytes, this copper is not available (3). It is tempting to speculate that CTR1 is uniquely positioned to make copper bioavailable either because it has a specific recognition mechanism and/or it is directly coupled to the copper chaperones that distribute copper for further utilization.After copper crosses the membrane, it is delivered to acceptor proteins by cytosolic metallochaperone...

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“…However, the mechanisms used and particularly the coordination of regulatory responses can vary significantly between species. Efflux mechanisms include the ubiquitous CopA/CopB P1-type ATPase transporters (44) and copper binding proteins, such as the CopZ family, which chaperone the copper ions intracellularly for incorporation/use by other copper binding proteins such as the efflux transporters (29). Most gram-negative bacteria also encode a multicopper oxidase (MCO), which is required for the periplasmic oxidation of Cu(I) to Cu(II) following P1-type ATPase transport of Cu(I) from the cytoplasm (31).…”

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confidence: 99%

Copper Stress Induces a Global Stress Response in Staphylococcus aureus and Represses sae and agr Expression and Biofilm Formation

Baker

Sitthisak

Sengupta

et al. 2010

Appl Environ Microbiol

133

104

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Copper is an important cofactor for many enzymes; however, high levels of copper are toxic. Therefore, bacteria must ensure there is sufficient copper for use as a cofactor but, more importantly, must limit free intracellular levels to prevent toxicity. In this study, we have used DNA microarray to identify Staphylococcus aureus copper-responsive genes. Transcriptional profiling of S. aureus SH1000 grown in excess copper identified a number of genes which fall into four groups, suggesting that S. aureus has four main mechanisms for adapting to high levels of environmental copper, as follows: (i) induction of direct copper homeostasis mechanisms; (ii) increased oxidative stress resistance; (iii) expression of the misfolded protein response; and (iv) repression of a number of transporters and global regulators such as Agr and Sae. Our experimental data confirm that resistance to oxidative stress and particularly to H 2 O 2 scavenging is an important S. aureus copper resistance mechanism. Our previous studies have demonstrated that Eap and Emp proteins, which are positively regulated by Agr and Sae, are required for biofilm formation under low-iron growth conditions. Our transcriptional analysis has confirmed that sae, agr, and eap are repressed under high-copper conditions and that biofilm formation is indeed repressed under high-copper conditions. Therefore, our results may provide an explanation for how copper films can prevent biofilm formation on catheters.

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The multi-layered regulation of copper translocating P-type ATPases

Cited by 63 publications

References 128 publications

The P-Type ATPase Superfamily

The P-Type ATPase Superfamily

Copper Transport in Mammalian Cells: Special Care for a Metal with Special Needs

Copper Stress Induces a Global Stress Response in Staphylococcus aureus and Represses sae and agr Expression and Biofilm Formation

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