Eating while intoxicated: characterizing the molecular mechanism behind V. cholerae toxin MakA-regulated autophagy
Dale P Corkery1,2, Yao-Wen Wu1,2
1Department of Chemistry, Umeå University, Umeå, Sweden.
Autophagy
|November 21, 2022
Abstract:
Extracellular pathogens utilize secreted virulence factors to regulate host cell function. Recently we characterized the molecular mechanism behind host macroautophagy/autophagy regulation by the Vibrio cholerae toxin MakA. Cholesterol binding at the plasma membrane induces MakA endocytosis and pH-dependent pore assembly. Membrane perforation of late endosomal membranes induces cellular membrane repair pathways and V-ATPase-dependent unconventional LC3 lipidation on damaged membranes.
Insights
The Vibrio cholerae toxin MakA regulates autophagy by forming pores in host cell membranes. This triggers membrane repair and unconventional LC3 lipidation on damaged endosomes.
Area of Science:
- Cell Biology
- Molecular Biology
- Microbiology
Background:
- Extracellular pathogens secrete virulence factors to manipulate host cell functions.
- The Vibrio cholerae toxin MakA's role in regulating host macroautophagy/autophagy was recently investigated.
Purpose of the Study:
- To elucidate the molecular mechanism by which MakA regulates autophagy.
- To understand how MakA induces membrane damage and subsequent host responses.
Main Methods:
- Characterization of MakA's interaction with cholesterol at the plasma membrane.
- Analysis of MakA endocytosis and pH-dependent pore formation.
- Investigation of V-ATPase-dependent unconventional LC3 lipidation on damaged membranes.
Main Results:
- Cholesterol binding initiates MakA endocytosis and pore assembly in late endosomes.
- Membrane perforation triggers host cell membrane repair pathways.
- V-ATPase mediates unconventional LC3 lipidation on damaged endosomal membranes.
Conclusions:
- MakA employs a novel mechanism to disrupt host autophagy.
- MakA-induced membrane damage activates specific cellular repair and lipidation pathways.
- Understanding MakA's action provides insights into pathogen-host interactions and autophagy regulation.
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