ArticleThe Journal of biological chemistry2011
Critical role of the beta-subunit CDC50A in the stable expression, assembly, subcellular localization, and lipid transport activity of the P4-ATPase ATP8A2.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Expanding the spectrum of ATP8A2 mutations: a new splicing variant and systematic review of CAMRQ4 syndrome.Molecular biology reports · 2025Pooled it
- Loss of Atp8a2 drives neurodegeneration through the dysregulation of spatiotemporal phosphatidylserine externalization in mature neurons.Cell death & disease · 2026Article
- Phospholipid flippases ATP8A1 and ATP8A2 regulate GABAiScience · 2026Article
- Repairing Atp10D in C57Bl/6J mice restores protein expression but does not mitigate metabolic stress from high fat diet.Scientific reports · 2026Article
- Leaflet-specific phospholipid imaging using genetically encoded proximity sensors.Nature chemical biology · 2026Article
- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
- Lipid flippases ATP9A and ATP9B form a complex and contribute to the exocytic pathway from the Golgi.Life science alliance · 2025Article
- Membrane asymmetry facilitates murine norovirus entry and persistent enteric infection.PLoS biology · 2025Article
- TAT-1, a phosphatidylserine flippase, affects molting and regulates membrane trafficking in the epidermis of Caenorhabditis elegans.Genetics · 2025Article
- Substrates, regulation, cellular functions, and disease associations of P4-ATPases.Communications biology · 2025Review
- Improved Broad Spectrum Antifungal Drug Synergies with Cryptomycin, a Cdc50-Inspired Antifungal Peptide.ACS infectious diseases · 2024Article
- A novel missense variant in the ATPase domain of ATP8A2 and review of phenotypic variability of ATP8A2-related disorders caused by missense changes.Neurogenetics · 2024Article
- The lipid flippase ATP8A1 regulates the recruitment of ARF effectors to the trans-Golgi Network.Archives of biochemistry and biophysics · 2024Article
- Consensus, controversies, and conundrums of P4-ATPases: The emerging face of eukaryotic lipid flippases.The Journal of biological chemistry · 2024Review
- Functional and in silico analysis of ATP8A2 and other P4-ATPase variants associated with human genetic diseases.Disease models & mechanisms · 2024Article
- A novel missense variant in the ATPase domain of ATP8A2 and review of phenotypic variability ofmedRxiv : the preprint server for health sciences · 2024Article
- Flipping the script: Advances in understanding how and why P4-ATPases flip lipid across membranes.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Article
- Reconstitution of ATP-dependent lipid transporters: gaining insight into molecular characteristics, regulation, and mechanisms.Bioscience reports · 2023Review
- Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
P(4)-ATPases have been implicated in the transport of lipids across cellular membranes. Some P(4)-ATPases are known to associate with members of the CDC50 protein family. Previously, we have shown that the P(4)-ATPase ATP8A2 purified from photoreceptor membranes and reconstituted into liposomes catalyzes the active transport of phosphatidylserine across membranes. However, it was unclear whether ATP8A2 functioned alone or as a complex with a CDC50 protein. Here, we show by mass spectrometry and Western blotting using newly generated anti-CDC50A antibodies that CDC50A is associated with ATP8A2 purified from photoreceptor membranes. ATP8A2 expressed in HEK293T cells assembles with endogenous or expressed CDC50A, but not CDC50B, to generate a heteromeric complex that actively transports phosphatidylserine and to a lesser extent phosphatidylethanolamine across membranes. Chimera CDC50 proteins in which various domains of CDC50B were replaced with the corresponding domains of CDC50A were used to identify domains important in the formation of a functional ATP8A2-CDC50 complex. These studies indicate that both the transmembrane and exocytoplasmic domains of CDC50A are required to generate a functionally active complex. The N-terminal cytoplasmic domain of CDC50A appears to play a direct role in the reaction cycle. Mutagenesis studies further indicate that the N-linked oligosaccharide chains of CDC50A are required for stable expression of an active ATP8A2-CDC50A lipid transport complex. Together, our studies indicate that CDC50A is the β-subunit of ATP8A2 and is crucial for the correct folding, stable expression, export from endoplasmic reticulum, and phosphatidylserine flippase activity of ATP8A2.
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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.