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ER-Golgi membrane contact sites control the formation of plasma membrane lipid nanodomains required for anthrax intoxication

ABSTRACT: To promote infections, pathogens exploit host cell machineries including structural elements of the plasma membrane. Studying these interactions and identifying molecular players is an ideal way to gain insights into the fundamental biology of the host cell. Here, we used the anthrax toxin to screen a library of 1500 regulatory, cell surface, and membrane trafficking genes for their involvement in the intoxication process. We found that ER-Golgi localized proteins TMED2 and TMED10 are required for toxin oligomerization at the plasma-membrane of human cells, an essential step dependant on localization to cholesterol-rich lipid nanodomains. Biochemical, morphological and mechanistic analyses showed that TMED2 and TMED10 are essential components of a complex that operates the exchange of both cholesterol and ceramides at ER-Golgi membrane contact sites. Overall, this study of anthrax intoxication led to the discovery that lipid compositional remodelling at ER-Golgi interfaces fully controls the formation of functional membrane nanodomains at the cell surface.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Muhammad Umair Anwar

LAB HEAD: F. Gisou van der Goot

PROVIDER: PXD036511 | Pride | 2022-09-07

REPOSITORIES: Pride

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