Thy-1 binds to integrin beta(3) on astrocytes and triggers formation of focal contact sites.

Détails

ID Serval
serval:BIB_29B0AC40A402
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Thy-1 binds to integrin beta(3) on astrocytes and triggers formation of focal contact sites.
Périodique
Current Biology
Auteur(s)
Leyton L., Schneider P., Labra C.V., Rüegg C., Hetz C.A., Quest A.F., Bron C.
ISSN
0960-9822[print], 0960-9822[linking]
Statut éditorial
Publié
Date de publication
2001
Volume
11
Numéro
13
Pages
1028-1038
Langue
anglais
Résumé
BACKGROUND: Thy-1 is an abundant neuronal glycoprotein in mammals. Despite such prevalence, Thy-1 function remains largely obscure in the absence of a defined ligand. Astrocytes, ubiquitous cells of the brain, express a putative Thy-1 ligand that prevents neurite outgrowth. In this paper, a ligand molecule for Thy-1 was identified, and the consequences of Thy-1 binding for astrocyte function were investigated. RESULTS: Thy-1 has been implicated in cell adhesion and, indeed, all known Thy-1 sequences were found to contain an integrin binding, RGD-like sequence. Thy-1 interaction with beta3 integrin on astrocytes was demonstrated in an adhesion assay using a thymoma line (EL-4) expressing high levels of Thy-1. EL-4 cells bound to astrocytes five times more readily than EL-4(-f), control cells lacking Thy-1. Binding was blocked by either anti-Thy-1 or anti-beta3 antibodies, by RGD-related peptides, or by soluble Thy-1-Fc chimeras. However, neither RGE/RLE peptides nor Thy-1(RLE)-Fc fusion protein inhibited the interaction. Immobilized Thy-1-Fc, but not Thy-1(RLE)-Fc fusion protein supported the attachment and spreading of astrocytes in a Mn(2+)-dependent manner. Binding to Thy-1-Fc was inhibited by RGD peptides. Moreover, vitronectin, fibrinogen, denatured collagen (dcollagen), and a kistrin-derived peptide, but not fibronectin, also mediated Mn(2+)-dependent adhesion, suggesting the involvement of beta3 integrin. The addition of Thy-1 to matrix-bound astrocytes induced recruitment of paxillin, vinculin, and focal adhesion kinase (FAK) to focal contacts and increased tyrosine phosphorylation of proteins such as p130(Cas) and FAK. Furthermore, astrocyte binding to immobilized Thy-1-Fc alone was sufficient to promote focal adhesion formation and phosphorylation on tyrosine. CONCLUSIONS: Thy-1 binds to beta3 integrin and triggers tyrosine phosphorylation of focal adhesion proteins in astrocytes, thereby promoting focal adhesion formation, cell attachment, and spreading.
Mots-clé
Amino Acid Sequence, Animals, Antibodies, Monoclonal/immunology, Antigens, CD/immunology, Antigens, CD/metabolism, Antigens, Thy-1/chemistry, Antigens, Thy-1/metabolism, Astrocytes/metabolism, Brain/metabolism, Cell Adhesion, Cells, Cultured, Cytoskeletal Proteins/metabolism, Extracellular Matrix Proteins/metabolism, Focal Adhesions/metabolism, Integrin beta3, Mice, Molecular Sequence Data, Neurons/metabolism, Oligopeptides/pharmacology, Phosphotyrosine/metabolism, Platelet Membrane Glycoproteins/immunology, Platelet Membrane Glycoproteins/metabolism, Rats, Sequence Homology, Amino Acid, Signal Transduction, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/01/2008 18:30
Dernière modification de la notice
20/08/2019 14:09
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