title: Integrin-mediated signaling induced by simian virus 40 leads to transient uncoupling of cortical actin and the plasma membrane.
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.
authors: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors: Lilli
authors: L
authors: Stergiou
authors: Manuel
authors: M
authors: Bauer
authors: Waltraud
authors: W
authors: Mair
authors: Damaris
authors: D
authors: Bausch-Fluck
authors: Nir
authors: N
authors: Drayman
authors: Bernd
authors: B
authors: Wollscheid
authors: Ariella
authors: A
authors: Oppenheim
authors: Lucas
authors: L
authors: Pelkmans
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004843:Epistasis, Genetic; D053263:Gene Regulatory Networks; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D027601:Polyomavirus Infections / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D040901:Proteomics; D051057:Proto-Oncogene Proteins c-akt; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034622:RNA Interference; D015398:Signal Transduction; D013539:Simian virus 40 / Q000502:physiology*; D053586:Virus Internalization; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099149:Ezrin
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D006028:Glycosphingolipids; D016023:Integrins; D008562:Membrane Glycoproteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D020742:rhoA GTP-Binding Protein; D000099149:Ezrin; C000631429:PDK1 protein, human