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Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins

Francisco Sarmento Mesquita1,2, Cláudia Brito1,2,3, Maria J Mazon Moya4

  • 1I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

EMBO Reports
|January 1, 2017
PubMed

Insights

The endoplasmic reticulum chaperone Gp96 regulates plasma membrane (PM) blebbing against bacterial pore-forming toxins (PFTs). Gp96 and NMHCIIA protect host cells and hosts from PFTs and Listeria monocytogenes infection.

Area of Science:

  • Cell Biology
  • Immunology
  • Microbiology

Background:

  • Plasma membrane (PM) blebbing is a host defense against bacterial pore-forming toxins (PFTs).
  • The precise regulation and impact of blebbing during infection remain incompletely understood.
  • PFTs can induce PM blebbing, but the underlying molecular mechanisms require further elucidation.

Purpose of the Study:

  • To identify novel regulators of PFT-induced plasma membrane blebbing.
  • To investigate the role of Gp96 and NMHCIIA in host cell protection against bacterial toxins.
  • To understand the impact of Gp96-NMHCIIA interaction on cellular processes during infection.

Main Methods:

  • Co-immunoprecipitation assays to identify protein interactions.
  • Live-cell imaging to observe plasma membrane blebbing dynamics.
  • Confocal microscopy to analyze cytoskeletal organization and protein localization.
  • In vivo studies to validate findings in a host organism.

Main Results:

  • Endoplasmic reticulum chaperone Gp96 was identified as a novel regulator of PFT-induced blebbing.
  • Gp96 interacts with non-muscle myosin heavy chain IIA (NMHCIIA), controlling its activity and remodeling for bleb formation and retraction.
  • Gp96 and NMHCIIA protect plasma membrane integrity from Listeria monocytogenes LLO, affecting cell migration and cytoskeletal organization.
  • The Gp96-NMHCIIA association was validated in vivo, with Gp96 essential for host protection against LLO-mediated killing.

Conclusions:

  • Gp96 is a critical regulator of PFT-induced plasma membrane blebbing by modulating NMHCIIA.
  • The Gp96-NMHCIIA complex plays a dual role in protecting host cells from bacterial toxins and influencing cellular dynamics.
  • Gp96 is essential for host defense against Listeria monocytogenes LLO, highlighting its in vivo importance.
Keywords:
Listeria monocytogenesactomyosinendoplasmic reticulum chaperoneplasma membrane blebbingpore‐forming toxins

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