title: VE-cadherin-induced Cdc42 signaling regulates formation of membrane protrusions in endothelial cells.
abstract: The cytoplasmic domain of cadherins and the associated catenins link the cytoskeleton with signal transduction pathways. To study the signaling function of non-junctional VE-cadherin, which can form during the loss VE-cadherin homotypic adhesion, wild type VE-cadherin or VE-cadherin cytoplasmic domain (DeltaEXD) was expressed in sub-confluent endothelial cells. We observed that Cdc42 was activated in transfected cells and that these cells also developed Cdc42-dependent >70-microm-long plasma membrane protrusions. The formation of these structures required actin polymerization, and they developed specifically in endothelial cells as compared with epithelial cells. Expression of the VE-cadherin cytoplasmic domain lacking the beta-catenin binding site also induced Cdc42 activation; thus, its activation cannot be ascribed to beta-catenin binding. However, these cells were not able to form the protrusions. These results suggest that the cytoplasmic domain of non-junctional VE-cadherin can serve as a scaffold involved in Cdc42 activation at the endothelial plasma membrane. beta-Catenin and the associated alpha-catenin may serve as support sites for actin polymerization, leading to formation of long plasma membrane protrusions. Thus, non-junctional VE-cadherin actively participates in inside-out signaling at the plasma membrane, leading to the development of endothelial membrane protrusions.
authors.affiliation: Department of Pharmacology, The University of Illinois College of Medicine, 835 S. Wolcott Avenue, M/C 868, Chicago, IL 60612, USA. pkouklis@uic.edu
authors.forename: Panos
authors.initials: P
authors.lastname: Kouklis
authors.forename: Maria
authors.initials: M
authors.lastname: Konstantoulaki
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000502:physiology*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000648:ultrastructure; D006801:Humans; D010750:Phosphoproteins / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D051176:beta Catenin; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*; D000095002:Delta Catenin; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D051176:beta Catenin; D020764:cdc42 GTP-Binding Protein; D000095002:Delta Catenin; D000099152:Cadherin 5; C495270:CTNNB1 protein, human