PMID:19723805

Citation	Avalos, AM, Valdivia, AD, Muñoz, N, Herrera-Molina, R, Tapia, JC, Lavandero, S, Chiong, M, Burridge, K, Schneider, P, Quest, AF and Leyton, L (2009) Neuronal Thy-1 induces astrocyte adhesion by engaging syndecan-4 in a cooperative interaction with alphavbeta3 integrin that activates PKCalpha and RhoA. J. Cell. Sci. 122:3462-71
Abstract	Clustering of alphavbeta3 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 PKCalpha implicated PKCalpha and RhoA activation in these events. Therefore, combined interaction of the astrocyte alphavbeta3-integrin-syndecan-4 receptor pair with Thy-1, promotes adhesion to the underlying matrix via PKCalpha- 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.
Links	PubMed PMC2746130 Online version:10.1242/jcs.034827
Keywords	Amino Acid Sequence; Animals; Antigens, Thy-1/chemistry; Antigens, Thy-1/genetics; Antigens, Thy-1/metabolism; Astrocytes/chemistry; Astrocytes/metabolism; Cell Adhesion; Cell Line; Enzyme Activation; Humans; Integrin alphaVbeta3/genetics; Integrin alphaVbeta3/metabolism; Molecular Sequence Data; Neurons/chemistry; Neurons/metabolism; Protein Binding; Protein Kinase C-alpha/genetics; Protein Kinase C-alpha/metabolism; Protein Structure, Tertiary; Rats; Sequence Alignment; Signal Transduction; Syndecan-4/genetics; Syndecan-4/metabolism; rhoA GTP-Binding Protein/genetics; rhoA GTP-Binding Protein/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:THY1		GO:0046777: protein autophosphorylation	ECO:0000314:		P		Fig. 2. Thy-1 stimulates FAK autophosphorylation	complete CACAO 5815
RAT:THY1	involved_in	GO:0046777: protein autophosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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