ArticleHuman molecular genetics2015
Direct interactions of adaptor protein complexes 1 and 2 with the copper transporter ATP7A mediate its anterograde and retrograde trafficking.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Wilson disease-causing mutations in the carboxyl terminus of ATP7B regulates its localization and Golgi exit selectively in the unpolarized cells.Metallomics : integrated biometal science · 2023Pooled it
- 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
- Copper in Human Health and Disease: Insights from Inherited Disorders.Physiology (Bethesda, Md.) · 2026Review
- Disorders Mimicking Wilson's Disease: Clinical, Biochemical, and Molecular Perspectives for Accurate Differential Diagnosis.Diagnostics (Basel, Switzerland) · 2026Review
- Acute GARP depletion disrupts vesicle transport, leading to severe defects in sorting, secretion, and O-glycosylation.bioRxiv : the preprint server for biology · 2024Article
- The physiological and pathophysiological roles of copper in the nervous system.The European journal of neuroscience · 2024Review
- Regulation of the apico-basolateral trafficking polarity of the homologous copper-ATPases ATP7A and ATP7B.Journal of cell science · 2024Article
- Early onset hereditary neuronopathies: an update on non-5q motor neuron diseases.Brain : a journal of neurology · 2023Review
- The interplay between copper metabolism and microbes: in perspective of host copper-dependent ATPases ATP7A/B.Frontiers in cellular and infection microbiology · 2023Review
- 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
- The M1311V variant of ATP7A is associated with impaired trafficking and copper homeostasis in models of motor neuron disease.Neurobiology of disease · 2021Article
- Early-onset Wilson disease caused byCold Spring Harbor molecular case studies · 2020Article
- Trafficking mechanisms of P-type ATPase copper transporters.Current opinion in cell biology · 2019Review
- The Endolysosomal System and Proteostasis: From Development to Degeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Review
- Cerebrospinal Fluid-Directed rAAV9-rsATP7A Plus Subcutaneous Copper Histidinate Advance Survival and Outcomes in a Menkes Disease Mouse Model.Molecular therapy. Methods & clinical development · 2018Article
- Interaction between the AAA ATPase p97/VCP and a concealed UBX domain in the copper transporter ATP7A is associated with motor neuron degeneration.The Journal of biological chemistry · 2018Article
- Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Article
- Multiple di-leucines in the ATP7A copper transporter are required for retrograde trafficking to the trans-Golgi network.Metallomics : integrated biometal science · 2016Article
- Copper trafficking to the secretory pathway.Metallomics : integrated biometal science · 2016Review
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
ATP7A is a P-type ATPase in which diverse mutations lead to X-linked recessive Menkes disease or occipital horn syndrome. Recently, two previously unknown ATP7A missense mutations, T994I and P1386S, were shown to cause an isolated distal motor neuropathy without clinical or biochemical features of other ATP7A disorders. These mutant alleles cause subtle defects in ATP7A intracellular trafficking, resulting in preferential plasma membrane localization compared with wild-type ATP7A. We reported previously that ATP7A(P1386S) causes unstable insertion of the eighth and final transmembrane segment, preventing proper position of the carboxyl-terminal tail in a proportion of mutant molecules. Here, we utilize this and other naturally occurring and engineered mutant ATP7A alleles to identify mechanisms of normal ATP7A trafficking. We show that adaptor protein (AP) complexes 1 and 2 physically interact with ATP7A and that binding is mediated in part by a carboxyl-terminal di-leucine motif. In contrast to other ATP7A missense mutations, ATP7A(P1386S) partially disturbs interactions with both APs, leading to abnormal axonal localization in transfected NSC-34 motor neurons and altered calcium-signaling following glutamate stimulation. Our results imply that AP-1 normally tethers ATP7A at the trans-Golgi network in the somatodendritic segments of motor neurons and that alterations affecting the ATP7A carboxyl-terminal tail induce release of the copper transporter to the axons or axonal membranes. The latter effects are intensified by diminished interaction with AP-2, impeding ATP7A retrograde trafficking. Taken together, these findings further illuminate the normal molecular mechanisms of ATP7A trafficking and suggest a pathophysiological basis for ATP7A-related distal motor neuropathy.
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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.