During infection, plasma membrane (PM) blebs protect host cells against bacterial pore‐forming toxins (PFTs), but were also proposed to promote pathogen dissemination. However, the details and impact of blebbing regulation during infection remained unclear. Here, we identify the endoplasmic reticulum chaperone Gp96 as a novel regulator of PFT‐induced blebbing. Gp96 interacts with non‐muscle myosin heavy chain IIA (NMHCIIA) and controls its activity and remodelling, which is required for appropriate coordination of bleb formation and retraction. This mechanism involves NMHCIIA–Gp96 interaction and their recruitment to PM blebs and strongly resembles retraction of uropod‐like structures from polarized migrating cells, a process that also promotes NMHCIIA–Gp96 association. Consistently, Gp96 and NMHCIIA not only protect the PM integrity from listeriolysin O (LLO) during infection by Listeria monocytogenes but also affect cytoskeletal organization and cell migration. Finally, we validate the association between Gp96 and NMHCIIA in vivo and show that Gp96 is required to protect hosts from LLO‐dependent killing.
Gp96 plays a role in actomyosin remodelling and coordination of plasma membrane blebbing triggered by pore‐forming toxins. This process protects membrane integrity and host survival during infection and has implications in cytoskeletal organization.
Gp96 controls NMHCIIA network and NMII activity during PFT‐induced PM blebbing.
Gp96 and NMHCIIA protect PM integrity against bacterial PFT‐mediated damage.
Gp96–NMHCIIA interplay during PFT responses resembles polarized cell migration process.
Gp96 promotes host survival during in vivo Listeria infection.
EMBO Reports (2017) 18: 303–318
- Received June 3, 2016.
- Revision received November 16, 2016.
- Accepted November 18, 2016.
- © 2016 The Authors
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