Identification of a Novel Cadherin (Vascular Endothelial Cadherin-2) Located at Intercellular Junctions in Endothelial Cells*
- From ‡Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy, ¶Commissariat àl’Energie Atomique, Laboratoire de Transgénèse et Différenciation Cellulaire, Département de Biologie Moléculaire et Structurale, 17 rue des Martyrs, 38054 Grenoble, France, and ‖Facoltà di Farmacologia, Universitàdegli Studi di Milano, Via Vanvitelli 32, 20129 Milano, Italy
Abstract
Endothelial cells express two major cadherins, VE- and N-cadherins, but only the former consistently participates in adherens junction organization. In heart microvascular endothelial cells, we identified a new member of the cadherin superfamily using polymerase chain reaction. The entire putative coding sequence was determined. Similarly to protocadherins, while the extracellular domain presented homology with other members of the cadherin superfamily, the intracellular region was unrelated either to cadherins or to any other known protein. We propose for this new protein the name of vascular endothelial cadherin-2. By Northern blot analysis, the mRNA was present only in cultured endothelial cell lines but not in other cell types such as NIH 3T3, Chinese hamster ovary, or L cells. In addition, mRNA was particularly abundant in highly vascularized organs such as lung or kidney. In endothelial cells and transfectants, this cadherin was unable to bind catenins and presented a weak association with the cytoskeleton. This new molecule shares some functional properties with VE-cadherin and other members of the cadherin family. In Chinese hamster ovary transfectants it promoted homotypic Ca2+ dependent aggregation and adhesion and clustered at intercellular junctions. However, in contrast to VE-cadherin, it did not modify paracellular permeability, cell migration, and density-dependent cell growth. These observations suggest that different cadherins may promote homophilic cell-to-cell adhesion but that the functional consequences of this interaction depend on their binding to specific intracellular signaling/cytoskeletal proteins.
Footnotes
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↵* This work was supported in part by Associazione Italiana per la Ricerca sul Cancro; European Community Projects BI04 CT 960036, BMH4 CT960669, and BMH4 CT 950875; and Human Frontier Science Program Project GR 0006/1997-M).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) Y08715.
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↵§ To whom correspondence should be addressed: Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy. Tel.: 39-2-390141; Fax: 39-2-3546277; E-mail: telo{at}irfmn.mnegri.it.
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↵1 The abbreviations used are: PECAM, platelet/endothelial cell adhesion molecule; CHO, Chinese hamster ovary; EC1–EC6 domains, extracellular domains 1–6; PCR, polymerase chain reaction; VE-cad, vascular endothelial cadherin; VE-cad-2, vascular endothelial cadherin 2; PBS, phosphate-buffered saline; mAb, monoclonal antibody; bp, base pair(s); kb, kilobase pair(s).
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↵2 P. Telo’, unpublished observations.
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- Received March 2, 1998.
- Revision received April 29, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
