气候变化领域集成服务门户(CCPortal): AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells

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DOI	10.1073/pnas.2025208118
	AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells
	Kook S.; Wang P.; Meng S.; Jetter C.S.; Sucre J.M.S.; Benjamin J.T.; Gokey J.J.; Hanby H.A.; Jaume A.; Goetzl L.; Marks M.S.; Guttentag S.H.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:20
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Endosome; Lung epithelium; Lysosome; Pulmonary fibrosis
语种	英语
scopus关键词	2 amino 3 phosphonopropionic acid; leucine; peroxiredoxin 6; transcription factor Yap1; adaptor protein; adenosine triphosphatase; ATP8A1 protein, human; phosphatidylserine; phospholipid transfer protein; Rab protein; Rab11 protein; signal transducing adaptor protein; transcription factor; YAP1 protein, human; animal cell; animal experiment; animal model; animal tissue; Article; carboxy terminal sequence; cell count; cell migration; controlled study; endosome; female; gain of function mutation; human; human cell; lamellar body; lung alveolus cell type 2; lung fibrosis; membrane leaflet; mouse; nonhuman; ocular albinism; priority journal; protein targeting; animal; C57BL mouse; cell line; cell motion; cytology; disease model; gene expression regulation; genetics; lung; lung alveolus epithelium cell; lysosome; male; metabolism; pathology; primary cell culture; signal transduction; transport at the cellular level; Adaptor Protein Complex 3; Adaptor Proteins, Signal Transducing; Adenosine Triphosphatases; Alveolar Epithelial Cells; Animals; Biological Transport; Cell Line; Cell Movement; Disease Models, Animal; Endosomes; Female; Gene Expression Regulation; Hermanski-Pudlak Syndrome; Humans; Lung; Lysosomes; Male; Mice; Mice, Inbred C57BL; Peroxiredoxin VI; Phosphatidylserines; Phospholipid Transfer Proteins; Primary Cell Culture; Pulmonary Fibrosis; rab GTP-Binding Proteins; Signal Transduction; Transcription Factors
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251179
作者单位	Department of Pediatrics, Division of Neonatology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Physiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, United States; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, United States
推荐引用方式 GB/T 7714	Kook S.,Wang P.,Meng S.,et al. AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells[J],2021,118(20).
APA	Kook S..,Wang P..,Meng S..,Jetter C.S..,Sucre J.M.S..,...&Guttentag S.H..(2021).AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells.Proceedings of the National Academy of Sciences of the United States of America,118(20).
MLA	Kook S.,et al."AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells".Proceedings of the National Academy of Sciences of the United States of America 118.20(2021).