Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion.
Details
Download: 1-s2.0-S2211124718311173-main.pdf (3187.32 [Ko])
State: Public
Version: Final published version
State: Public
Version: Final published version
Serval ID
serval:BIB_0F426EF76306
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion.
Journal
Cell Reports
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
24
Number
6
Pages
1425-1433
Language
english
Abstract
IL-1β requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1β secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1β secretion by pyroptotic and non-pyroptotic cells, and the precise functions of caspase-1 and GSDMD therein, are unresolved. Here, we show that, while efficient early secretion of endogenous IL-1β from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1β release in vitro and in vivo proceeds independently of GSDMD. IL-1β maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1β from resting, non-pyroptotic macrophages, but the speed of IL-1β release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1β cleavage induces IL-1β enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1β secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1β trafficking facilitates its unconventional secretion.
Keywords
caspase-1, gasdermin, inflammasome, interleukin-1, macrophage, neutrophil, phosphoinositides, pyroptosis, trafficking, unconventional protein secretion
Pubmed
Web of science
Open Access
Yes
Create date
29/08/2018 7:46
Last modification date
20/08/2019 13:36