ArticleThe EMBO journal1996
Ligand-regulated transport of the Menkes copper P-type ATPase efflux pump from the Golgi apparatus to the plasma membrane: a novel mechanism of regulated trafficking.
Article in The EMBO journal, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers.
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Who cites it
207 citing papers in PubMed, 641 citations in OpenAlex.
- Copper oxide nanoparticles: from EU-regulatory landscape and mechanistic toxicity towards a cuproptosis-linked adverse outcome pathway.Archives of toxicology · 2026Review
- Copper, cuproptosis, and cancer: biology concepts of a novel cell death.Apoptosis : an international journal on programmed cell death · 2026Review
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Engineering cuproptosis with nanomedicine: Design, combination therapy, and translation in cancer.Materials today. Bio · 2026Review
- SLC25A3 exports mitochondrial copper to metalate cytochromeProceedings of the National Academy of Sciences of the United States of America · 2026Article
- A functional framework in patient fibroblasts informs ATP7A variant pathogenicity and identifies p.Q990P as a novel cause of distal motor neuropathy.Human molecular genetics · 2026Article
- A broad-spectrum inhibitor of copper-exporting PProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Copper in Human Health and Disease: Insights from Inherited Disorders.Physiology (Bethesda, Md.) · 2026Review
- The interactions of copper, glutamate, and cuproptosis: insights into brain health and Alzheimer's disease pathology.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Review
- Copper restriction unmasks axonal degeneration in a mouse model of X-linked hereditary motor neuropathy.Metallomics : integrated biometal science · 2026Article
- A First-In-Class Broad Spectrum Inhibitor of Copper Exporting PbioRxiv : the preprint server for biology · 2026Article
- Copper Homeostasis and Cuproptosis in Neurological Disorders.Drug design, development and therapy · 2026Review
- The Copper Chaperone ATOX1 Exhibits Differential Protein-Protein Interactions and Contributes to Skeletal Myoblast Differentiation.Molecular and cellular biology · 2026Article
- Carnosine Biofunctionalized Hydroxyapatite Induces Copper-Driven Osteogenesis and Angiogenesis, Strengthening Its Bone Regenerative Capacities.ACS biomaterials science & engineering · 2025Article
- RAD23B acquires a copper metalloadaptor function in amphibian-to-reptile evolution to increase metabolism and regulate genomic integrity.Molecular cell · 2025Article
- A primer on copper biology in the brain.Neurobiology of disease · 2025Review
- The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer.Signal transduction and targeted therapy · 2025Review
- Copper in cancer: friend or foe? Metabolism, dysregulation, and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- The petunia heavy metal P-type ATPase PhHMA5II1 interacts with copper chaperons and regulate Cu detoxification.Plant cell reports · 2025Article
147 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Menkes P-type ATPase (MNK), encoded by the Menkes gene (MNK; ATP7A), is a transmembrane copper-translocating pump which is defective in the human disorder of copper metabolism, Menkes disease. Recent evidence that the MNK P-type ATPase has a role in copper efflux has come from studies using copper-resistant variants of cultured Chinese hamster ovary (CHO) cells. These variants have MNK gene amplification and consequently overexpress MNK, the extents of which correlate with the degree of elevated copper efflux. Here, we report on the localization of MNK in these copper-resistant CHO cells when cultured in different levels of copper. Immunofluorescence studies demonstrated that MNK is predominantly localized to the Golgi apparatus of cells in basal medium. In elevated copper conditions there was a rapid trafficking of MNK from the Golgi to the plasma membrane. This shift in steady-state distribution of MNK was reversible and not dependent on new protein synthesis. In media containing basal copper, MNK accumulated in cytoplasmic vesicles after treatment of cells with a variety of agents that inhibit endosomal recycling. We suggest that MNK continuously recycles between the Golgi and the plasma membrane and elevated copper shifts the steady-state distribution from the Golgi to the plasma membrane. These data reveal a novel system of regulated protein trafficking which ultimately leads to the efflux of an essential yet potentially toxic ligand, where the ligand itself appears directly and specifically to stimulate the trafficking of its own transporter.
Indexed as
Identifiers
8947031PMC452430W192250034What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.