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PMID: 7698986 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The molecular organization of endothelial cell to cell junctions: differential association of plakoglobin, beta-catenin, and alpha-catenin with vascular endothelial cadherin (VE-cadherin).

The Journal of cell biology ·Vol. 129 ·No. 1 ·1995-04-00 ·Pages 203-17

Lampugnani MG, Corada M, Caveda L, Breviario F, Ayalon O, Geiger B, Dejana E

Abstract

In this paper we report that the assembly of interendothelial junctions containing the cell type-specific vascular endothelial cadherin (VE-cadherin or cadherin-5) is a dynamic process which is affected by the functional state of the cells. Immunofluorescence double labeling of endothelial cells (EC) cultures indicated that VE-cadherin, alpha-catenin, and beta-catenin colocalized in areas of cell to cell contact both in sparse and confluent EC monolayers. In contrast, plakoglobin became associated with cell-cell junctions only in tightly confluent cells concomitantly with an increase in its protein and mRNA levels. Furthermore, the amount of plakoglobin coimmunoprecipitated with VE-cadherin, increased in closely packed monolayers. Artificial wounding of confluent EC monolayers resulted in a major reorganization of VE-cadherin, alpha-catenin, beta-catenin, and plakoglobin. All these proteins decreased in intensity at the boundaries of EC migrating into the lesion. In contrast, EC located immediately behind the migrating front retained junctional VE-cadherin, alpha-catenin, and beta-catenin while plakoglobin was absent from these sites. In line with this observation, the amount of plakoglobin coimmunoprecipitated with VE-cadherin decreased in migrating EC. These data suggest that VE-cadherin, alpha-catenin, and beta-catenin are already associated with each other at early stages of intercellular adhesion and become readily organized at nascant cell contacts. Plakoglobin, on the other hand, associates with junctions only when cells approach confluence. When cells migrate, this order is reversed, namely, plakoglobin dissociates first and, then, VE-cadherin, alpha-catenin, and beta-catenin disassemble from the junctions. The late association of plakoglobin with junctions suggests that while VE-cadherin/alpha-catenin/beta-catenin complex can function as an early recognition mechanism between EC, the formation of mature, cytoskeleton-bound junctions requires plakoglobin synthesis and organization.

MeSH Terms
Blotting, Northern Blotting, Western Cadherins/analysis,biosynthesis Cell Adhesion Molecules/analysis Cells, Cultured Cytoskeletal Proteins/analysis,biosynthesis Desmoplakins Electrophoresis, Polyacrylamide Gel Endothelium, Vascular/physiology,ultrastructure Fluorescent Antibody Technique Humans Intercellular Junctions/physiology,ultrastructure Kinetics Molecular Weight Time Factors Trans-Activators Umbilical Veins alpha Catenin beta Catenin gamma Catenin
Chemicals
CTNNA1 protein, human CTNNB1 protein, human Cadherins Cell Adhesion Molecules Cytoskeletal Proteins Desmoplakins Trans-Activators alpha Catenin beta Catenin gamma Catenin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lampugnani M G
Laboratory of Vascular Biology, Mario Negri Institute for Pharmacological Research, Milano, Italy.
Corada M
Caveda L
Breviario F
Ayalon O
Geiger B
Dejana E
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.129.1.203
Published
1995-04-00
Pages
203-17
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120375
Subset
IM
Grants
Telethon · A.003 · Italy
External Links
PubMed source DOI: 10.1083/jcb.129.1.203 PMC Full Text View journal details
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