ATP release due to Thy-1-integrin binding induces P2X7-mediated calcium entry required for focal adhesion formation.

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Serval ID
serval:BIB_74A830962970
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ATP release due to Thy-1-integrin binding induces P2X7-mediated calcium entry required for focal adhesion formation.
Journal
Journal of Cell Science
Author(s)
Henríquez M., Herrera-Molina R., Valdivia A., Alvarez A., Kong M., Muñoz N., Eisner V., Jaimovich E., Schneider P., Quest A.F., Leyton L.
ISSN
1477-9137 (Electronic)
ISSN-L
0021-9533
Publication state
Published
Issued date
2011
Volume
124
Number
Pt 9
Pages
1581-1588
Language
english
Abstract
Thy-1, an abundant mammalian glycoprotein, interacts with αvβ3 integrin and syndecan-4 in astrocytes and thus triggers signaling events that involve RhoA and its effector p160ROCK, thereby increasing astrocyte adhesion to the extracellular matrix. The signaling cascade includes calcium-dependent activation of protein kinase Cα upstream of Rho; however, what causes the intracellular calcium transients required to promote adhesion remains unclear. Purinergic P2X7 receptors are important for astrocyte function and form large non-selective cation pores upon binding to their ligand, ATP. Thus, we evaluated whether the intracellular calcium required for Thy-1-induced cell adhesion stems from influx mediated by ATP-activated P2X7 receptors. Results show that adhesion induced by the fusion protein Thy-1-Fc was preceded by both ATP release and sustained intracellular calcium elevation. Elimination of extracellular ATP with Apyrase, chelation of extracellular calcium with EGTA, or inhibition of P2X7 with oxidized ATP, all individually blocked intracellular calcium increase and Thy-1-stimulated adhesion. Moreover, Thy-1 mutated in the integrin-binding site did not trigger ATP release, and silencing of P2X7 with specific siRNA blocked Thy-1-induced adhesion. This study is the first to demonstrate a functional link between αvβ3 integrin and P2X7 receptors, and to reveal an important, hitherto unanticipated, role for P2X7 in calcium-dependent signaling required for Thy-1-stimulated astrocyte adhesion.
Keywords
Adenosine Triphosphate/metabolism, Animals, Antigens, Thy-1/genetics, Antigens, Thy-1/metabolism, Astrocytes/metabolism, Blotting, Western, Calcium/metabolism, Cell Line, Fluorescent Antibody Technique, Indirect, Focal Adhesions/metabolism, Integrins/genetics, Integrins/metabolism, Rats, Receptors, Purinergic P2X7/genetics, Receptors, Purinergic P2X7/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
07/09/2011 10:52
Last modification date
18/01/2020 7:09
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