title: Segregation of VE-cadherin from the LBRC depends on the   ectodomain sequence required for homophilic adhesion.
abstract: The lateral border recycling compartment (LBRC) is a reticulum ofperijunctional tubulovesicular membrane that is continuous with the plasmalemma of endothelial cells and is essential for efficient transendothelial migration (TEM) of leukocytes. The LBRC contains molecules involved in TEM, such as PECAM, PVR and CD99, but not VE-cadherin. Despite its importance, how membrane proteins are included in or excluded from the LBRC is not known. Immunoelectronmicroscopy and biochemical approaches demonstrate that inclusion into the LBRC is the default pathway for transmembrane molecules present at endothelial cell borders. A chimeric molecule composed of the extracellular domain of VE-cadherin and cytoplasmic tail of PECAM (VE-CAD/PECAM) did not enter the LBRC, suggesting that VE-cadherin was excluded by a mechanism involving its extracellular domain. Deletion of the homophilic interaction domain EC1 or the homophilic interaction motif RVDAE allowed VE-CAD/PECAM and even native VE-cadherin to enter the LBRC. Similarly, treatment with RVDAE peptide to block homophilic VE-cadherin interactions allowed endogenous VE-cadherin to enter the LBRC. This suggests that homophilic interactions of VE-cadherin stabilize it at cell borders and prevent entry into the LBRC.
authors.forename: Gong
authors.initials: G
authors.lastname: Feng
authors.forename: David P
authors.initials: DP
authors.lastname: Sullivan
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.forename: William A
authors.initials: WA
authors.lastname: Muller
mesh_terms: D000071443:12E7 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002449:Cell Aggregation / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology; D003593:Cytoplasm / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007739:L Cells; D007962:Leukocytes / Q000502:physiology; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000235:genetics*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000099152:Cadherin 5
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; D015820:Cadherins; D015815:Cell Adhesion Molecules; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011991:Receptors, Virus; D000099152:Cadherin 5; C061828:CD99 protein, human; C066100:poliovirus receptor