ArticleMolecular biology of the cell2021
PLEKHA5, PLEKHA6, and PLEKHA7 bind to PDZD11 to target the Menkes ATPase ATP7A to the cell periphery and regulate copper homeostasis.
Article in Molecular biology of the cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 37 citations in OpenAlex.
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- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Targeting CDK1 and copper homeostasis in breast cancer via a nanopolymer drug delivery system.Cell biology and toxicology · 2024Article
- Redistribution of PU.1 partner transcription factor RUNX1 binding secures cell survival during leukemogenesis.The EMBO journal · 2024Article
- Acute GARP depletion disrupts vesicle transport, leading to severe defects in sorting, secretion, and O-glycosylation.bioRxiv : the preprint server for biology · 2024Article
- A phosphorylation-controlled switch confers cell cycle-dependent protein relocalization.Nature cell biology · 2024Article
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- Cingulin-nonmuscle myosin interaction plays a role in epithelial morphogenesis and cingulin nanoscale organization.Journal of cell science · 2024Article
- Resolving the three-dimensional interactome of Human Accelerated Regions during human and chimpanzee neurodevelopment.bioRxiv : the preprint server for biology · 2024Article
- A phosphorylation-controlled switch confers cell cycle-dependent protein relocalization.bioRxiv : the preprint server for biology · 2024Article
- Small-Molecule Fluorescent Probes for Binding- and Activity-Based Sensing of Redox-Active Biological Metals.Chemical reviews · 2024Review
- Paracingulin recruits CAMSAP3 to tight junctions and regulates microtubule and polarized epithelial cell organization.Journal of cell science · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Copper homeostasis is crucial for cellular physiology and development, and its dysregulation leads to disease. The Menkes ATPase ATP7A plays a key role in copper efflux, by trafficking from the Golgi to the plasma membrane upon cell exposure to elevated copper, but the mechanisms that target ATP7A to the cell periphery are poorly understood. PDZD11 interacts with the C-terminus of ATP7A, which contains sequences involved in ATP7A trafficking, but the role of PDZD11 in ATP7A localization is unknown. Here we identify PLEKHA5 and PLEKHA6 as new interactors of PDZD11 that bind to the PDZD11 N-terminus through their WW domains similarly to the junctional protein PLEKHA7. Using CRISPR-KO kidney epithelial cells, we show by immunofluorescence microscopy that WW-PLEKHAs (PLEKHA5, PLEKHA6, PLEKHA7) recruit PDZD11 to distinct plasma membrane localizations and that they are required for the efficient anterograde targeting of ATP7A to the cell periphery in elevated copper conditions. Pull-down experiments show that WW-PLEKHAs promote PDZD11 interaction with the C-terminus of ATP7A. However, WW-PLEKHAs and PDZD11 are not necessary for ATP7A Golgi localization in basal copper, ATP7A copper-induced exit from the Golgi, and ATP7A retrograde trafficking to the Golgi. Finally, measuring bioavailable and total cellular copper, metallothionein-1 expression, and cell viability shows that WW-PLEKHAs and PDZD11 are required for maintaining low intracellular copper levels when cells are exposed to elevated copper. These data indicate that WW-PLEKHAs-PDZD11 complexes regulate the localization and function of ATP7A to promote copper extrusion in elevated copper.
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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 Socratic graph.