ArticleProceedings of the National Academy of Sciences of the United States of America2021
AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Sustained YAP/TAZ activation promotes aberrant alveolar epithelial cell differentiation and drives persistent fibrotic remodeling.JCI insight · 2026Article
- A dileucine motif in TMEM163 is essential for its binding with both AP-3 and BLOC-1 complex.The Journal of biological chemistry · 2026Article
- Bothrops jararaca snake venom: A reappraisal of its coagulant activity in humans, mice, and rats.PLoS neglected tropical diseases · 2026Article
- Targeted inhibition of PARP-1 in pulmonary epithelial cells and macrophages via SPA-functionalized microparticles attenuates sepsis-induced lung injury.Materials today. Bio · 2026Article
- Divergent pathways of surfactant protein C maturation for disease-associated isoforms.The Journal of biological chemistry · 2026Article
- Lipid droplet-mitochondria contact sites as druggable spatial-pharmacology targets in respiratory disease: cross-cell-type mechanisms and translational strategies.Frontiers in cell and developmental biology · 2026Review
- Divergent Pathways of Surfactant Protein C Maturation for Disease-Associated Isoforms.bioRxiv : the preprint server for biology · 2025Article
- Review
- ATP8A1-translocated endosomal phosphatidylserine fine-tunes the multivesicular body formation and the endo-lysosomal traffic.iScience · 2025Article
- Emergence of inflammatory fibroblasts with aging in Hermansky-Pudlak syndrome associated pulmonary fibrosis.Communications biology · 2025Article
- Substrates, regulation, cellular functions, and disease associations of P4-ATPases.Communications biology · 2025Review
- Pathogenesis and Therapy of Hermansky-Pudlak Syndrome (HPS)-Associated Pulmonary Fibrosis.International journal of molecular sciences · 2024Review
- Article
- The lipid flippase ATP8A1 regulates the recruitment of ARF effectors to the trans-Golgi Network.Archives of biochemistry and biophysics · 2024Article
- Article
- Flipping the script: Advances in understanding how and why P4-ATPases flip lipid across membranes.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Alveolar Organoids in Lung Disease Modeling.Biomolecules · 2024Review
- UniTmp: unified resources for transmembrane proteins.Nucleic acids research · 2024Article
- Deficiency of the lipid flippase ATP10A causes diet-induced dyslipidemia in female mice.Scientific reports · 2024Article
- PPP1R12A is a recycling endosomal phosphatase that facilitates YAP activation.Scientific reports · 2023Article
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12 authors at 3 institutions in 1 country.
Funding
Abstract
Lamellar bodies (LBs) are lysosome-related organelles (LROs) of surfactant-producing alveolar type 2 (AT2) cells of the distal lung epithelium. Trafficking pathways to LBs have been understudied but are likely critical to AT2 cell homeostasis given associations between genetic defects of endosome to LRO trafficking and pulmonary fibrosis in Hermansky Pudlak syndrome (HPS). Our prior studies uncovered a role for AP-3, defective in HPS type 2, in trafficking Peroxiredoxin-6 to LBs. We now show that the P4-type ATPase ATP8A1 is sorted by AP-3 from early endosomes to LBs through recognition of a C-terminal dileucine-based signal. Disruption of the AP-3/ATP8A1 interaction causes ATP8A1 accumulation in early sorting and/or recycling endosomes, enhancing phosphatidylserine exposure on the cytosolic leaflet. This in turn promotes activation of Yes-activating protein, a transcriptional coactivator, augmenting cell migration and AT2 cell numbers. Together, these studies illuminate a mechanism whereby loss of AP-3-mediated trafficking contributes to a toxic gain-of-function that results in enhanced and sustained activation of a repair pathway associated with pulmonary fibrosis.
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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.