VE-cadherin-induced Cdc42 signaling regulates formation of membrane protrusions in endothelial cells.
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.
Kouklis
Panos
P
Department of Pharmacology, The University of Illinois College of Medicine, 835 S. Wolcott Avenue, M/C 868, Chicago, IL 60612, USA. pkouklis@uic.edu
Konstantoulaki
Maria
M
Malik
Asrar B
AB
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
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