ArticleMolecular biology of the cell2013
Trafficking of the Menkes copper transporter ATP7A is regulated by clathrin-, AP-2-, AP-1-, and Rab22-dependent steps.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
- 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
- Copper in Human Health and Disease: Insights from Inherited Disorders.Physiology (Bethesda, Md.) · 2026Review
- Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025Review
- The study of miRNA-211 affects melanogenesis progress in Cashmere goats via suppressingArchives animal breeding · 2025Article
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- When less is more - a fast TurboID knock-in approach for high-sensitivity endogenous interactome mapping.Journal of cell science · 2024Article
- Regulation of the apico-basolateral trafficking polarity of the homologous copper-ATPases ATP7A and ATP7B.Journal of cell science · 2024Article
- Carboplatin-induced upregulation of pan β-tubulin and class III β-tubulin is implicated in acquired resistance and cross-resistance of ovarian cancer.Cellular and molecular life sciences : CMLS · 2023Article
- Review
- KIF13A-A Key Regulator of Recycling Endosome Dynamics.Frontiers in cell and developmental biology · 2022Review
- Crossroads between membrane trafficking machinery and copper homeostasis in the nerve system.Open biology · 2021Review
- PLEKHA5, PLEKHA6, and PLEKHA7 bind to PDZD11 to target the Menkes ATPase ATP7A to the cell periphery and regulate copper homeostasis.Molecular biology of the cell · 2021Article
- Dynamic and cell-specific transport networks for intracellular copper ions.Journal of cell science · 2021Review
- Melanosome Biogenesis in the Pigmentation of Mammalian Skin.Integrative and comparative biology · 2021Review
- The M1311V variant of ATP7A is associated with impaired trafficking and copper homeostasis in models of motor neuron disease.Neurobiology of disease · 2021Article
- Copper metabolism as a unique vulnerability in cancer.Biochimica et biophysica acta. Molecular cell research · 2021Review
- The Clathrin adaptor AP-1 and Stratum act in parallel pathways to control Notch activation inDevelopment (Cambridge, England) · 2021Article
- Serotonin Receptor and Transporter Endocytosis Is an Important Factor in the Cellular Basis of Depression and Anxiety.Frontiers in cellular neuroscience · 2021Article
- Homozygous Loss-of-Function Mutations in AP1B1, Encoding Beta-1 Subunit of Adaptor-Related Protein Complex 1, Cause MEDNIK-like Syndrome.American journal of human genetics · 2019Article
- Trafficking mechanisms of P-type ATPase copper transporters.Current opinion in cell biology · 2019Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The transporter ATP7A mediates systemic copper absorption and provides cuproenzymes in the trans-Golgi network (TGN) with copper. To regulate metal homeostasis, ATP7A constitutively cycles between the TGN and plasma membrane (PM). ATP7A trafficking to the PM is elevated in response to increased copper load and is reversed when copper concentrations are lowered. Molecular mechanisms underlying this trafficking are poorly understood. We assess the role of clathrin, adaptor complexes, lipid rafts, and Rab22a in an attempt to decipher the regulatory proteins involved in ATP7A cycling. While RNA interference (RNAi)-mediated depletion of caveolin 1/2 or flotillin had no effect on ATP7A localization, clathrin heavy chain depletion or expression of AP180 dominant-negative mutant not only disrupted clathrin-regulated pathways, but also blocked PM-to-TGN internalization of ATP7A. Depletion of the μ subunits of either adaptor protein-2 (AP-2) or AP-1 using RNAi further provides evidence that both clathrin adaptors are important for trafficking of ATP7A from the PM to the TGN. Expression of the GTP-locked Rab22aQ64L mutant caused fragmentation of TGN membrane domains enriched for ATP7A. These appear to be a subdomain of the mammalian TGN, showing only partial overlap with the TGN marker golgin-97. Of importance, ATP7A remained in the Rab22aQ64L-generated structures after copper treatment and washout, suggesting that forward trafficking out of this compartment was blocked. This study provides evidence that multiple membrane-associated factors, including clathrin, AP-2, AP-1, and Rab22, are regulators of ATP7A trafficking.
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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.