title: Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with alpha3 beta1 integrin localized at endothelial lateral junctions.
abstract: Cell-to-cell junction structures play a key role in cell growth rate control and cell polarization. In endothelial cells (EC), these structures are also involved in regulation of vascular permeability and leukocyte extravasation. To identify novel components in EC intercellular junctions, mAbs against these cells were produced and selected using a morphological screening by immunofluorescence microscopy. Two novel mAbs, LIA1/1 and VJ1/16, specifically recognized a 25-kD protein that was selectively localized at cell-cell junctions of EC, both in the primary formation of cell monolayers and when EC reorganized in the process of wound healing. This antigen corresponded to the recently cloned platelet-endothelial tetraspan antigen CD151/PETA-3 (platelet-endothelial tetraspan antigen-3), and was consistently detected at EC cell-cell contact sites. In addition to CD151/PETA-3, two other members of the tetraspan superfamily, CD9 and CD81/ TAPA-1 (target of antiproliferative antibody-1), localized at endothelial cell-to-cell junctions. Biochemical analysis demonstrated molecular associations among tetraspan molecules themselves and those of CD151/ PETA-3 and CD9 with alpha3 beta1 integrin. Interestingly, mAbs directed to both CD151/PETA-3 and CD81/ TAPA-1 as well as mAb specific for alpha3 integrin, were able to inhibit the migration of ECs in the process of wound healing. The engagement of CD151/PETA-3 and CD81/TAPA-1 inhibited the movement of individual ECs, as determined by quantitative time-lapse video microscopy studies. Furthermore, mAbs against the CD151/PETA-3 molecule diminished the rate of EC invasion into collagen gels. In addition, these mAbs were able to increase the adhesion of EC to extracellular matrix proteins. Together these results indicate that CD81/TAPA-1 and CD151/PETA-3 tetraspan molecules are components of the endothelial lateral junctions implicated in the regulation of cell motility, either directly or by modulation of the function of the associated integrin heterodimers.
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid.
authors.forename: M
authors.initials: M
authors.lastname: Yáñez-Mó
authors.forename: A
authors.initials: A
authors.lastname: Alfranca
authors.forename: C
authors.initials: C
authors.lastname: Cabañas
authors.forename: M
authors.initials: M
authors.lastname: Marazuela
authors.forename: R
authors.initials: R
authors.lastname: Tejedor
authors.forename: M A
authors.initials: MA
authors.lastname: Ursa
authors.forename: L K
authors.initials: LK
authors.lastname: Ashman
authors.forename: M O
authors.initials: MO
authors.lastname: de Landázuri
authors.forename: F
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D005109:Extracellular Matrix; D005782:Gels; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000502:physiology*; D007365:Intercellular Junctions / Q000502:physiology*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D060185:Tetraspanin 24; D060225:Tetraspanin 28; D060245:Tetraspanin 29
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554715:CD151 protein, human; C554798:CD81 protein, human; C554869:CD9 protein, human; C554716:Cd151 protein, mouse; C554799:Cd81 protein, mouse; C554870:Cd9 protein, mouse; D005782:Gels; D039201:Integrin alpha3beta1; D016023:Integrins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D060185:Tetraspanin 24; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D003094:Collagen