Neuronal Thy-1 induces astrocyte adhesion by engaging syndecan-4 in a cooperative interaction with ?v?3 integrin that activates PKC? and RhoA

Avalos A.M.; Valdivia A.D.; Muñoz, N.; Herrera-Molina, R; Quest, A.F.G.; Leyton, L; Tapia, J.C.; Lavandero S.; Chiong M.; Burridge, K; Schneider, P.

Keywords: sequence, acid, neurons, rat, adhesion, enzyme, activation, tertiary, animals, binding, antigen, rats, protein, cell, mutant, matrix, line, site, humans, transduction, receptor, astrocytes, astrocyte, heparin, interaction, inhibitor, signal, alignment, molecular, integrin, data, article, kinase, syndecan, guanine, thy-1, vitronectin, rhoa, syndecan-4, controlled, animal, c, study, 4, 1, nucleotide, amino, priority, nonhuman, journal, Antigens,, extracellular, Structure,, GTP-Binding, C-alpha, focal, Thy, alphaVbeta3

Abstract

Clustering of ?v?3 integrin after interaction with the RGD-like integrin-binding sequence present in neuronal Thy-1 triggers formation of focal adhesions and stress fibers in astrocytes via RhoA activation. A putative heparin-binding domain is present in Thy-1, raising the possibility that this membrane protein stimulates astrocyte adhesion via engagement of an integrin and the proteoglycan syndecan-4. Indeed, heparin, heparitinase treatment and mutation of the Thy-1 heparin-binding site each inhibited Thy-1-induced RhoA activation, as well as formation of focal adhesions and stress fibers in DI TNC 1 astrocytes. These responses required both syndecan-4 binding and signaling, as evidenced by silencing syndecan-4 expression and by overexpressing a syndecan-4 mutant lacking the intracellular domain, respectively. Furthermore, lack of RhoA activation and astrocyte responses in the presence of a PKC inhibitor or a dominant-negative form of PKC? implicated PKC? and RhoA activation in these events. Therefore, combined interaction of the astrocyte ?v?3-integrin-syndecan-4 receptor pair with Thy-1, promotes adhesion to the underlying matrix via PKC?-and RhoA-dependent pathways. Importantly, signaling events triggered by such receptor cooperation are shown here to be the consequence of cell-cell rather than cell-matrix interactions. These observations are likely to be of widespread biological relevance because Thy-1-integrin binding is reportedly relevant to melanoma invasion, monocyte transmigration through endothelial cells and host defense mechanisms.

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Título de la Revista: JOURNAL OF CELL SCIENCE
Volumen: 122
Número: 19
Editorial: COMPANY BIOLOGISTS LTD
Fecha de publicación: 2009
Página de inicio: 3462
Página final: 3471
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-70350371490&partnerID=q2rCbXpz