Journal
JOURNAL OF CELL SCIENCE
Volume 122, Issue 19, Pages 3462-3471Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.034827
Keywords
Thy-1; Syndecan-4; Cell adhesion; Astrocytes
Categories
Funding
- Fogarty International Center-NIH [1R03TW006024-1, 1R03TW007810-01A1]
- FONDECYT [1040390, 1070699, 3050037, 11070116]
- NIH [GM-29860]
- FONDAP [15010006]
- ICGEB [CRP/CH100-05]
- CONICYT
- Swiss National Science Foundation
- Centro Fondap de Regulacion Celular y Patologia, P. Universidad Catolica de Chile, Santiago, Chile
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Clustering of alpha v beta 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 TNC1 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 alpha implicated PKC alpha and RhoA
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