Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_241083E0FA4C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria.
Journal
Nature communications
Author(s)
Santos J.C., Boucher D., Schneider L.K., Demarco B., Dilucca M., Shkarina K., Heilig R., Chen K.W., Lim RYH, Broz P.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
24/06/2020
Peer-reviewed
Oui
Volume
11
Number
1
Pages
3276
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The human non-canonical inflammasome controls caspase-4 activation and gasdermin-D-dependent pyroptosis in response to cytosolic bacterial lipopolysaccharide (LPS). Since LPS binds and oligomerizes caspase-4, the pathway is thought to proceed without dedicated LPS sensors or an activation platform. Here we report that interferon-induced guanylate-binding proteins (GBPs) are required for non-canonical inflammasome activation by cytosolic Salmonella or upon cytosolic delivery of LPS. GBP1 associates with the surface of cytosolic Salmonella seconds after bacterial escape from their vacuole, initiating the recruitment of GBP2-4 to assemble a GBP coat. The GBP coat then promotes the recruitment of caspase-4 to the bacterial surface and caspase activation, in absence of bacteriolysis. Mechanistically, GBP1 binds LPS with high affinity through electrostatic interactions. Our findings indicate that in human epithelial cells GBP1 acts as a cytosolic LPS sensor and assembles a platform for caspase-4 recruitment and activation at LPS-containing membranes as the first step of non-canonical inflammasome signaling.
Pubmed
Open Access
Yes
Create date
03/07/2020 17:29
Last modification date
30/04/2021 6:08
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