ArticleThe Journal of biological chemistry2016
Phosphatidic Acid Produced by RalA-activated PLD2 Stimulates Caveolae-mediated Endocytosis and Trafficking in Endothelial Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- The Blood-prostate Barrier: An Obstacle to Drug Delivery into the Prostate.Current drug delivery · 2025Review
- The role of transcytosis in the blood-retina barrier: from pathophysiological functions to drug delivery.Frontiers in pharmacology · 2025Review
- The dynamic regulatory network of phosphatidic acid metabolism: a spotlight on substrate cycling between phosphatidic acid and diacylglycerol.Biochemical Society transactions · 2024Review
- Article
- Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy.Redox biology · 2022Article
- Review
- Endothelial Transcytosis in Acute Lung Injury: Emerging Mechanisms and Therapeutic Approaches.Frontiers in physiology · 2022Review
- Cholesterol Sequestration from Caveolae/Lipid Rafts Enhances Cationic Liposome-Mediated Nucleic Acid Delivery into Endothelial Cells.Molecules (Basel, Switzerland) · 2021Article
- Filamin A Regulates Cardiovascular Remodeling.International journal of molecular sciences · 2021Review
- Article
- Oncogenic RAS drives the CRAF-dependent extracellular vesicle uptake mechanism coupled with metastasis.Journal of extracellular vesicles · 2021Article
- Wnt/β-catenin signaling: Structure, assembly and endocytosis of the signalosome.Development, growth & differentiation · 2021Review
- Design, Synthesis, and Biological Evaluation of Pyrano[2,3-c]-pyrazole-Based RalA Inhibitors Against Hepatocellular Carcinoma.Frontiers in chemistry · 2021Article
- Phospholipase D2 restores endothelial barrier function by promoting PTPN14-mediated VE-cadherin dephosphorylation.The Journal of biological chemistry · 2020Article
- Lung Endothelial Transcytosis.Comprehensive Physiology · 2020Review
- Control of endothelial tubulogenesis by Rab and Ral GTPases, and apical targeting of caveolin-1-labeled vacuoles.PloS one · 2020Article
- RAL GTPases Drive Intestinal Stem Cell Function and Regeneration through Internalization of WNT Signalosomes.Cell stem cell · 2019Article
- Exosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- AtCAP2 is crucial for lytic vacuole biogenesis during germination by positively regulating vacuolar protein trafficking.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Caveolae are the primary route for internalization and transendothelial transport of macromolecules, such as insulin and albumin. Caveolae-mediated endocytosis is activated by Src-dependent caveolin-1 (Cav-1) phosphorylation and subsequent recruitment of dynamin-2 and filamin A (FilA), which facilitate vesicle fission and trafficking, respectively. Here, we tested the role of RalA and phospholipase D (PLD) signaling in the regulation of caveolae-mediated endocytosis and trafficking. The addition of albumin to human lung microvascular endothelial cells induced the activation of RalA within minutes, and siRNA-mediated down-regulation of RalA abolished fluorescent BSA uptake. Co-immunoprecipitation studies revealed that albumin induced the association between RalA, Cav-1, and FilA; however, RalA knockdown with siRNA did not affect FilA recruitment to Cav-1, suggesting that RalA was not required for FilA and Cav-1 complex formation. Rather, RalA probably facilitates caveolae-mediated endocytosis by activating downstream effectors. PLD2 was shown to be activated by RalA, and inhibition of PLD2 abolished Alexa-488-BSA uptake, indicating that phosphatidic acid (PA) generated by PLD2 may facilitate caveolae-mediated endocytosis. Furthermore, using a PA biosensor, GFP-PASS, we observed that BSA induced an increase in PA co-localization with Cav-1-RFP, which could be blocked by a dominant negative PLD2 mutant. Total internal reflection fluorescence microscopy studies of Cav-1-RFP also showed that fusion of caveolae with the basal plasma membrane was dependent on PLD2 activity. Thus, our results suggest that the small GTPase RalA plays an important role in promoting invagination and trafficking of caveolae, not by potentiating the association between Cav-1 and FilA but by stimulating PLD2-mediated generation of phosphatidic acid.
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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.