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Integrin-Mediated Signaling Induced by Simian Virus 40 Leads to Transient Uncoupling of Cortical Actin and the Plasma Membrane


Stergiou, Lilli; Bauer, Manuel; Mair, Waltraud; Bausch-Fluck, Damaris; Drayman, Nir; Wollscheid, Bernd; Oppenheim, Ariella; Pelkmans, Lucas (2013). Integrin-Mediated Signaling Induced by Simian Virus 40 Leads to Transient Uncoupling of Cortical Actin and the Plasma Membrane. PLoS ONE, 8(2):e55799.

Abstract

Simian Virus 40 (SV40) is a paradigm pathogen with multivalent binding sites for the sphingolipid GM1, via which it induces its endocytosis for infection. Here we report that SV40 also utilizes cell surface integrins to activate signaling networks required for infection, even in the absence of the previously implicated glycosphingolipids. We identify ILK, PDK1, the RhoGAP GRAF1 and RhoA as core nodes of the signaling network activated upon SV40 engagement of integrins. We show that integrin-mediated signaling through host SV40 engagement induces the de-phosphorylation of Ezrin leading to uncoupling of the plasma membrane and cortical actin. Our results provide functional evidence for a mechanism by which SV40 activates signal transduction in human epithelial cells via integrins in the context of clathrin-independent endocytosis.

Abstract

Simian Virus 40 (SV40) is a paradigm pathogen with multivalent binding sites for the sphingolipid GM1, via which it induces its endocytosis for infection. Here we report that SV40 also utilizes cell surface integrins to activate signaling networks required for infection, even in the absence of the previously implicated glycosphingolipids. We identify ILK, PDK1, the RhoGAP GRAF1 and RhoA as core nodes of the signaling network activated upon SV40 engagement of integrins. We show that integrin-mediated signaling through host SV40 engagement induces the de-phosphorylation of Ezrin leading to uncoupling of the plasma membrane and cortical actin. Our results provide functional evidence for a mechanism by which SV40 activates signal transduction in human epithelial cells via integrins in the context of clathrin-independent endocytosis.

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Item Type:Journal Article, refereed, original work
Communities & Collections:Special Collections > SystemsX.ch
Special Collections > SystemsX.ch > Research, Technology and Development Projects > InfectX
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2013
Deposited On:21 Sep 2013 12:46
Last Modified:05 Aug 2017 11:40
Publisher:Public Library of Science (PLoS)
ISSN:1932-6203
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1371/journal.pone.0055799
PubMed ID:23409046

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