Brooks, A.B.E., Humphreys, D. orcid.org/0000-0002-1038-2538, Singh, V. et al. (4 more authors)
(2017)
MYO6 is targeted by Salmonella virulence effectors to trigger PI3-Kinase signalling and pathogen invasion into host cells.
Proceedings of the National Academy of Sciences, 114 (15).
pp. 3915-3920.
Abstract
To establish infections, Salmonella injects 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 the Salmonella effector 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) in Salmonella invasion. 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © National Academy of Sciences, 2017. This is an author produced version of a paper subsequently published in Proceedings of the National Academy of Sciences. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | motor protein; type 3 secretion system; rho GTPase; macropinocytosis; infection |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL MR/M011771/2 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Mar 2017 10:04 |
Last Modified: | 03 Apr 2019 12:26 |
Published Version: | https://doi.org/10.1073/pnas.1616418114 |
Status: | Published |
Publisher: | National Academy of Sciences |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.1616418114 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:114049 |