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Authordc.contributor.authorÁlvarez, Álvaro 
Authordc.contributor.authorLagos Cabré, Raúl 
Authordc.contributor.authorKong, Milene 
Authordc.contributor.authorCárdenas, Areli 
Authordc.contributor.authorBurgos Bravo, Francesca 
Authordc.contributor.authorSchneider, Pascal 
Authordc.contributor.authorQuest, Andrew F. G. 
Authordc.contributor.authorLeyton Campos, Lisette 
Cita de ítemdc.identifier.citationBiochimica et Biophysica Acta 1863 (2016) 2175–2188es_ES
Abstractdc.description.abstractOur previous reports indicate that ligand-induced alpha(v)beta(3) integrin and Syndecan-4 engagement increases focal adhesion formation and migration of astrocytes. Additionally, ligated integrins trigger ATP release through unknown mechanisms, activating P2X7 receptors (P2X7R), and the uptake of Ca2+ to promote cell adhesion. However, whether the activation of P2X7R and ATP release are required for astrocyte migration and whether alpha(v)beta(3) integrin and Syndecan-4 receptors communicate with P2X7R via ATP remains unknown. Here, cells were stimulated with Thy-1, a reported alpha(v)beta(3) integrin and Syndecan-4 ligand. Results obtained indicate that ATP was released by Thy-1 upon integrin engagement and required the participation of phosphatidylinositol-3-kinase (PI3K), phospholipase-C gamma (PLC-gamma) and inositol trisphosphate (IP3) receptors (IP3R). IP3R activation leads to increased intracellular Ca2+, hemichannel (Connexin-43 and Pannexin-1) opening, and ATP release. Moreover, silencing of the P2X7R or addition of hemichannel blockers precluded Thy-I-induced astrocyte migration. Finally, Thy-1 lacking the integrin-binding site did not stimulate ATP release, whereas Thy-1 mutated in the Syndecan-4-binding domain increased ATP release, albeit to a lesser extent and with delayed kinetics compared to wild-type Thy-1. Thus, hemichannels activated downstream of an alpha(v)beta(3) integrin-PI3K-PLC gamma-IP3R pathway are responsible for Thy-1-induced, hemichannel-mediated and Syndecan-4-modulated ATP release that transactivates P2X7Rs to induce Ca2+ entry. These findings uncover a hitherto unrecognized role for hemichannels in the regulation of astrocyte migration via P2X7R transactivation induced by integrin-mediated ATP release.es_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.uri*
Sourcedc.sourceBiochimica et Biophysica Actaes_ES
Keywordsdc.subjectCell migrationes_ES
Títulodc.titleIntegrin-mediated transactivation of P2X7R via hemichannel-dependent ATP release stimulates astrocyte migrationes_ES
Document typedc.typeArtículo de revista
Indexationuchile.indexArtículo de publicación ISIes_ES

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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile