title: MYO6 is targeted bySalmonellavirulence effectors to trigger PI3-kinase signaling and pathogen invasion into host cells.
abstract: To establish infections,Salmonellainjects virulence effectors that hijack the host actin cytoskeleton and phosphoinositide signaling to drive pathogen invasion. How effectors reprogram the cytoskeleton network remains unclear. By reconstituting the activities of theSalmonellaeffector SopE, we recapitulated Rho GTPase-driven actin polymerization at model phospholipid membrane bilayers in cell-free extracts and identified the network of Rho-recruited cytoskeleton proteins. Knockdown of network components revealed a key role for myosin VI (MYO6) inSalmonellainvasion. SopE triggered MYO6 localization to invasion foci, and SopE-mediated activation of PAK recruited MYO6 to actin-rich membranes. We show that the virulence effector SopB requires MYO6 to regulate the localization of PIP3 and PI(3)P phosphoinositides and Akt activation. SopE and SopB target MYO6 to coordinate phosphoinositide production at invasion foci, facilitating the recruitment of cytoskeleton adaptor proteins to mediate pathogen uptake.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1TN, United Kingdom.
authors.forename: Andrew B E
authors.initials: AB
authors.lastname: Brooks
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1TN, United Kingdom.|Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Humphreys
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1TN, United Kingdom.
authors.forename: Vikash
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1TN, United Kingdom.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Davidson
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Arden
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom fb207@cam.ac.uk vk103@cam.ac.uk.
authors.forename: Folma
authors.initials: F
authors.lastname: Buss
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1TN, United Kingdom; fb207@cam.ac.uk vk103@cam.ac.uk.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Koronakis
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000382:microbiology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D012486:Salmonella typhimurium / Q000378:metabolism / Q000472:pathogenicity*; D015398:Signal Transduction; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C485164:FGD4 protein, human; D008840:Microfilament Proteins; D010716:Phosphatidylinositols; C103987:SopE protein, Salmonella; D037521:Virulence Factors; C089785:myosin VI; D058539:Phosphatidylinositol 3-Kinase; C489224:SopB protein, Salmonella; D018995:Myosin Heavy Chains
keywords: infection; macropinocytosis; motor protein; rho GTPase; type 3 secretion system