Posttranslational regulation of copper transporters

Berghe, Peter V. E. van den; Klomp, Leo W. J.

doi:10.1007/s00775-009-0592-7

Cited by 53 publications

(38 citation statements)

References 129 publications

(185 reference statements)

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“…CTR1 is particularly expressed in the intestinal cells, in the endothelial cells of brain capillaries, in choroid plexus and brain parenchyma [28]. CTR1 is a transmembrane carrier, which may shift easily between plasma membrane and intra-cellular vesicles [29]. It is estimated that the uptake of at least 80% of the copper is controlled by the carrier [30].…”

Section: The Atpases Atp7a/atp7b Ctr1 and Chaperonesmentioning

confidence: 99%

Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

Manto

2014

Toxics

103

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As a cofactor of proteins and enzymes involved in critical molecular pathways in mammals and low eukaryotes, copper is a transition metal essential for life. The intra-cellular and extra-cellular metabolism of copper is under tight control, in order to maintain free copper concentrations at very low levels. Copper is a critical element for major neuronal functions, and the central nervous system is a major target of disorders of copper metabolism. Both the accumulation of copper and copper deficiency are associated with brain dysfunction. The redox capacities of free copper, its ability to trigger the production of reactive oxygen species and the close relationships with the regulation of iron and zinc are remarkable features. Major advances in our understanding of the relationships between copper, neuronal functions and neurodegeneration have occurred these last two decades. The metabolism of copper and the current knowledge on the consequences of copper dysregulation on brain disorders are reviewed, with a focus on neurodegenerative diseases, such as Wilson's disease, Alzheimer's disease and Parkinson's disease. In vitro studies, in vivo experiments and evidence from clinical observations of the neurotoxic effects of copper provide the basis for future therapies targeting copper homeostasis.

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Section: The Atpases Atp7a/atp7b Ctr1 and Chaperonesmentioning

confidence: 99%

Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

Manto

2014

Toxics

103

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“…YS and WIF-B cells (ϳ10 7 /dish and 0.5-0. 8 ϫ 10 7 /dish, respectively) were scraped into 500 l of lysis buffer B.…”

Section: Methodsmentioning

confidence: 99%

Communication between the N and C Termini Is Required for Copper-stimulated Ser/Thr Phosphorylation of Cu(I)-ATPase (ATP7B)

Braiterman

Gupta

Chaerkady

et al. 2015

Journal of Biological Chemistry

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Background:Copper levels stimulate trafficking and hyperphosphorylation of the copper transporter ATP7B. Results: Hyperphosphorylation can occur prior to exit from the TGN and requires intact N and C terminus but is not required for apically directed trafficking. Conclusion: Copper-stimulated hyperphosphorylation of ATP7B occurs on the C terminus. Significance: Hyperphosphorylation and apically directed trafficking are independent events.

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“…Mutation of the corresponding genes in Menkes disease (ATP7A) (Online Mendelian Inheritance in Man (OMIM) 309400) and Wilson disease (ATP7B) (OMIM 277900) leads to systemic Cu deficiency and liver Cu toxicosis, respectively (3). The expression and activity of ATP7A and ATP7B are regulated by a variety of physiological stimuli in addition to Cu as well as posttranslational modifications and protein-protein interactions (13,14).…”

mentioning

confidence: 99%

Role of Glutaredoxin1 and Glutathione in Regulating the Activity of the Copper-transporting P-type ATPases, ATP7A and ATP7B

Singleton

McInnes

Cater

et al. 2010

Journal of Biological Chemistry

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The copper-transporting P-type ATPases (Cu-ATPases), ATP7A and ATP7B, are essential for the regulation of intracellular copper homeostasis. In this report we describe new roles for glutathione (GSH) and glutaredoxin1 (GRX1) in Cu homeostasis through their regulation of Cu-ATPase activity. GRX1 is a thiol oxidoreductase that catalyzes the reversible reduction of GSH-mixed disulfides to their respective sulfhydryls (deglutathionylation). Here, we demonstrated that glutathionylation of the Cu-ATPases and their interaction with GRX1 were affected by alterations in Cu levels. The data support our hypothesis that the Cu-ATPases serve as substrates for Cu-dependent GRX1-mediated deglutathionylation. This in turn liberates the CuATPase cysteinyl thiol groups for Cu binding and transport. GSH depletion experiments led to reversible inhibition of the Cu-ATPases that correlated with effects on intracellular Cu levels and GRX1 activity. Finally, knockdown of GRX1 expression resulted in an increase in intracellular Cu accumulation. Together, these data directly implicate GSH and GRX1 with important new roles in redox regulation of the Cu-ATPases, through modulation of Cu binding by the Cu-ATPase cysteine motifs.

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Posttranslational regulation of copper transporters

Cited by 53 publications

References 129 publications

Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

Communication between the N and C Termini Is Required for Copper-stimulated Ser/Thr Phosphorylation of Cu(I)-ATPase (ATP7B)

Role of Glutaredoxin1 and Glutathione in Regulating the Activity of the Copper-transporting P-type ATPases, ATP7A and ATP7B

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