Role of cadherins and plakoglobin in interendothelial adhesion under resting conditions and shear stress.
The role of cadherins and the cadherin-binding cytosolic protein plakoglobin in intercellular adhesion was studied in cultured human umbilical venous endothelial cells exposed to fluid shear stress. Extracellular Ca2+ depletion (< 10(-7) M) caused the disappearance of both cadherins and plakoglobin from junctions, whereas the distribution of platelet endothelial cell adhesion molecule 1 (PECAM-1) remained unchanged. Cells stayed fully attached to each other for several hours in low Ca2+ but began to dissociate under flow conditions. At the time of recalcification, vascular endothelial (VE) cadherin and beta-catenin became first visible at junctions, followed by plakoglobin with a delay of approximately 20 min. Full fluid shear stress stability of the junctions correlated with the time course of the reappearance of plakoglobin. Inhibition of plakoglobin expression by microinjection of antisense oligonucleotides did not interfere with the junctional association of VE-cadherin, PECAM-1, and beta-catenin. The plakoglobin-deficient cells remained fully attached to each other under resting conditions but began to dissociate in response to flow. Shear stress-induced junctional dissociation was also observed in cultures of plakoglobin-depleted arterial endothelial cells of the porcine pulmonary trunk. These observations show that interendothelial adhesion under hydrodynamic but not resting conditions requires the junctional location of cadherins associated with plakoglobin. beta-Catenin cannot functionally compensate for the junctional loss of plakoglobin, and PECAM-1-mediated adhesion is not sufficient for monolayer integrity under flow.
Schnittler
H J
HJ
Institute of Anatomy, University of Würzburg, Germany.
Püschel
B
B
Drenckhahn
D
D
D015703:Antigens, CD; D015820:Cadherins / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000502:physiology*; D051180:Desmoplakins; D004533:Egtazic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology; D013314:Stress, Mechanical; D015534:Trans-Activators; D014471:Umbilical Veins; D051176:beta Catenin; D051185:gamma Catenin; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D002118:Calcium; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D004533:Egtazic Acid; D016376:Oligonucleotides, Antisense; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin; D000099152:Cadherin 5; C495270:CTNNB1 protein, human