ArticleThe Journal of biological chemistry2014
Heparan sulfates mediate the interaction between platelet endothelial cell adhesion molecule-1 (PECAM-1) and the Gαq/11 subunits of heterotrimeric G proteins.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Nanoscopy reveals heparan sulfate clusters as docking sites for SARS-CoV-2 attachment and entry.eLife · 2026Article
- Nanoscopy Reveals Heparan Sulfate Clusters as Docking Sites for SARS-CoV-2 Attachment and Entry.bioRxiv : the preprint server for biology · 2025Article
- Syndecans modulate ghrelin receptor signaling.Journal of molecular endocrinology · 2025Article
- Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions.The EMBO journal · 2024Article
- Glycosaminoglycans: Participants in Microvascular Coagulation of Sepsis.Thrombosis and haemostasis · 2024Review
- Low or oscillatory shear stress and endothelial permeability in atherosclerosis.Frontiers in physiology · 2024Review
- Mechanisms of endothelial flow sensing.Nature cardiovascular research · 2023Review
- Vascular mechanotransduction.Physiological reviews · 2023Review
- Leptomeningeal anastomoses: Mechanisms of pial collateral remodeling in ischemic stroke.WIREs mechanisms of disease · 2022Review
- Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production.Scientific reports · 2021Article
- The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases.Cardiovascular engineering and technology · 2021Review
- Mechanobiology of Microvascular Function and Structure in Health and Disease: Focus on the Coronary Circulation.Frontiers in physiology · 2021Review
- The hydromechanics in arteriogenesis.Aging medicine (Milton (N.S.W)) · 2020Review
- Impairment of Flow-Sensitive Inwardly Rectifying KArteriosclerosis, thrombosis, and vascular biology · 2020Article
- Rapid flow-induced activation of GαAmerican journal of physiology. Cell physiology · 2019Article
- The Role of Midkine in Arteriogenesis, Involving Mechanosensing, Endothelial Cell Proliferation, and Vasodilation.International journal of molecular sciences · 2018Review
- Molecular mechanisms for enhancement of stromal cell-derived factor 1-induced chemotaxis by platelet endothelial cell adhesion molecule 1 (PECAM-1).The Journal of biological chemistry · 2017Article
- IPCellular and molecular life sciences : CMLS · 2017Review
- Endothelial Glycocalyx-Mediated Nitric Oxide Production in Response to Selective AFM Pulling.Biophysical journal · 2017Article
- Shear stress induces GαAmerican journal of physiology. Cell physiology · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The endothelial cell-cell junction has emerged as a major cell signaling structure that responds to shear stress by eliciting the activation of signaling pathways. Platelet endothelial cell adhesion molecule-1 (PECAM-1) and heterotrimeric G protein subunits Gαq and 11 (Gαq/11) are junctional proteins that have been independently proposed as mechanosensors. Our previous findings suggest that they form a mechanosensitive junctional complex that discriminates between different flow profiles. The nature of the PECAM-1·Gαq/11 interaction is still unclear although it is likely an indirect association. Here, we investigated the role of heparan sulfates (HS) in mediating this interaction and in regulating downstream signaling in response to flow. Co-immunoprecipitation studies show that PECAM-1·Gαq/11 binding is dramatically decreased by competitive inhibition with heparin, pharmacological inhibition with the HS antagonist surfen, and enzymatic removal of HS chains with heparinase III treatment as well as by site-directed mutagenesis of basic residues within the extracellular domain of PECAM-1. Using an in situ proximity ligation assay, we show that endogenous PECAM-1·Gαq/11 interactions in endothelial cells are disrupted by both competitive inhibition and HS degradation. Furthermore, we identified the heparan sulfate proteoglycan syndecan-1 in complexes with PECAM-1 that are rapidly decreased in response to flow. Finally, we demonstrate that flow-induced Akt activation is attenuated in endothelial cells in which PECAM-1 was knocked down and reconstituted with a binding mutant. Taken together, our results indicate that the PECAM-1·Gαq/11 mechanosensitive complex contains an endogenous heparan sulfate proteoglycan with HS chains that is critical for junctional complex assembly and regulating the flow response.
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