Catenin-dependent and -independent Functions of Vascular Endothelial Cadherin

doi:10.1074/jbc.270.52.30965

Catenin-dependent and -independent Functions of Vascular Endothelial Cadherin (*)

From the (1)Istituto di Ricerche Farmacologiche Mario Negri, 20157-Milano, Italia,
(2)Institute of Cellular Biology and Pathology, Bucharest-79691, Romania, and
(3)CEA, Laboratoire d'Hématologie, INSERM U217, DBMS, CEN/Grenoble, France

^§Supported by a postdoctoral fellowship of the European Community (Contract ERBCHBICT930374). To whom correspondence should be addressed:
Istituto di Ricerche, Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italia.
Tel.: 39-2-39014477; Fax: 39-2-3546277; Pilar{at}imimnvx.irfmn.mnegri.it.

Abstract

Vascular endothelial cadherin (VE-cadherin, cadherin-5, or 7B4) is an endothelial specific cadherin that regulates cell to cell junction organization in this cell type. Cadherin linkage to intracellular catenins was found to be required for their adhesive properties and for localization at cell to cell junctions. We constructed a mutant form of VE-cadherin lacking the last 82 amino acids of the cytoplasmic domain. Surprisingly, despite any detectable association of this truncated VE-cadherin to catenin-cytoskeletal complex, the molecule was able to cluster at cell-cell contacts in a manner similar to wild type VE-cadherin. Truncated VE-cadherin was also able to promote calcium-dependent cell to cell aggregation and to partially inhibit cell detachment and migration from a confluent monolayer. In contrast, intercellular junction permeability to high molecular weight molecules was severely impaired by truncation of VE-cadherin cytoplasmic domain. These results suggest that the VE-cadherin extracellular domain is enough for early steps of cell adhesion and recognition. However, interaction of VE-cadherin with the cytoskeleton is necessary to provide strength and cohesion to the junction. The data also suggest that cadherin functional regulation might not be identical among the members of the family.

Footnotes

↵^¶ On leave of absence from the Center of Pharmaceutical Chemistry, Havana, Cuba.
↵* This work was supported in part by the Italian National Research Council (special project Applicazioni Cliniche della Ricerca Oncologica) and the Associazione Italiana per la Ricerca sul Cancro. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵⁽¹⁾ The abbreviations used are:

VE-cadherin

vascular endothelial cadherin

CHO

Chinese hamster ovary

mAb

monoclonal antibody

PBS

phosphate-buffered saline

TBS

Tris-buffered saline

kb

kilobase pair(s).
↵⁽²⁾ P. Navarro, L. Caveda, F. Breviario, I. Mândoteanu, M.-G. Lampugnani, and E. Dejana, unpublished results.
- Received June 13, 1995.
- Revision received September 20, 1995.