ArticleSmall GTPases2020
Multiple Rap1 effectors control Epac1-mediated tightening of endothelial junctions.
Article in Small GTPases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- VE-cadherin interaction proteomics identifies ARVCF as stabilizer of endothelial adherens junctions.iScience · 2026Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Divergent Functions of Rap1A and Rap1B in Endothelial Biology and Disease.International journal of molecular sciences · 2025Review
- ATP depletion in anthrax edema toxin pathogenesis.PLoS pathogens · 2025Article
- The dual Ras-association domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis.Journal of cell science · 2024Article
- Adenylate cyclase activates the cAMP signalling pathway to enhance platelet-rich plasma-treated Achilles tendon disease, a theoretical bioinformatics-based study.World journal of orthopedics · 2024Article
- Rap1 in the Context of PCSK9, Atherosclerosis, and Diabetes.Current atherosclerosis reports · 2023Review
- Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Shear stress control of vascular leaks and atheromas through Tie2 activation by VE-PTP sequestration.EMBO molecular medicine · 2023Article
- Rap1 regulates apical contractility to allow embryonic morphogenesis without tissue disruption and acts in part via Canoe-independent mechanisms.Molecular biology of the cell · 2023Article
- ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Identification of guanine nucleotide exchange factors that increase Cdc42 activity in primary human endothelial cells.Small GTPases · 2021Article
- Article
- Integration of Rap1 and Calcium Signaling.International journal of molecular sciences · 2020Review
- Selective small-molecule EPAC activators.Biochemical Society transactions · 2019Review
- VE-PTP inhibition stabilizes endothelial junctions by activating FGD5.EMBO reports · 2019Article
- Small GTPase Rap1A/B Is Required for Lymphatic Development and Adrenomedullin-Induced Stabilization of Lymphatic Endothelial Junctions.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epac1 and Rap1 mediate cAMP-induced tightening of endothelial junctions. We have previously found that one of the mechanisms is the inhibition of Rho-mediated tension in radial stress fibers by recruiting the RhoGAP ArhGAP29 in a complex containing the Rap1 effectors Rasip1 and Radil. However, other mechanisms have been proposed as well, most notably the induction of tension in circumferential actin cables by Cdc42 and its GEF FGD5. Here, we have investigated how Rap1 controls FGD5/Cdc42 and how this interconnects with Radil/Rasip1/ArhGAP29. Using endothelial barrier measurements, we show that Rho inhibition is not sufficient to explain the barrier stimulating effect of Rap1. Indeed, Cdc42-mediated tension is induced at cell-cell contacts upon Rap1 activation and this is required for endothelial barrier function. Depletion of potential Rap1 effectors identifies AF6 to mediate Rap1 enhanced tension and concomitant Rho-independent barrier function. When overexpressed in HEK293T cells, AF6 is found in a complex with FGD5 and Radil. From these results we conclude that Rap1 utilizes multiple pathways to control tightening of endothelial junctions, possibly through a multiprotein effector complex, in which AF6 functions to induce tension in circumferential actin cables.
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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.