Right place, right time: Localisation and assembly of the NLRP3 inflammasome
File(s)
OA Location
Author(s)
Hamilton, Claire
Anand, Paras K
Type
Journal Article
Abstract
The NLRP3 inflammasome is a multimeric protein complex that cleaves
caspase-1 and the pro-inflammatory cytokines interleukin 1 beta (IL-1β)
and IL-18. Dysregulated NLRP3 inflammasome signalling is linked to
several chronic inflammatory and autoimmune conditions; thus,
understanding the activation mechanisms of the NLRP3 inflammasome is
essential. Studies over the past few years have implicated vital roles for
distinct intracellular organelles in both the localisation and assembly of the NLRP3 inflammasome. However, conflicting reports exist. Prior to its
activation, NLRP3 has been shown to be resident in the endoplasmic
reticulum (ER) and cytosol, although, upon activation, the NLRP3
inflammasome has been shown to assemble in the cytosol, mitochondria,
and mitochondria-associated ER membranes by different reports. Finally,
very recent work has suggested that NLRP3 may be localised on or
adjacent to the Golgi apparatus and that release of mediators from this
organelle may contribute to inflammasome assembly. Therefore, NLRP3
may be strategically placed on or in close proximity to these subcellular
compartments to both sense danger signals originating from these
organelles and use the compartment as a scaffold to assemble the
complex. Understanding where and when NLRP3 inflammasome assembly occurs may help identify potential targets for treatment of NLRP3-related disorders.
caspase-1 and the pro-inflammatory cytokines interleukin 1 beta (IL-1β)
and IL-18. Dysregulated NLRP3 inflammasome signalling is linked to
several chronic inflammatory and autoimmune conditions; thus,
understanding the activation mechanisms of the NLRP3 inflammasome is
essential. Studies over the past few years have implicated vital roles for
distinct intracellular organelles in both the localisation and assembly of the NLRP3 inflammasome. However, conflicting reports exist. Prior to its
activation, NLRP3 has been shown to be resident in the endoplasmic
reticulum (ER) and cytosol, although, upon activation, the NLRP3
inflammasome has been shown to assemble in the cytosol, mitochondria,
and mitochondria-associated ER membranes by different reports. Finally,
very recent work has suggested that NLRP3 may be localised on or
adjacent to the Golgi apparatus and that release of mediators from this
organelle may contribute to inflammasome assembly. Therefore, NLRP3
may be strategically placed on or in close proximity to these subcellular
compartments to both sense danger signals originating from these
organelles and use the compartment as a scaffold to assemble the
complex. Understanding where and when NLRP3 inflammasome assembly occurs may help identify potential targets for treatment of NLRP3-related disorders.
Date Issued
2019-05-17
Date Acceptance
2019-04-02
Citation
F1000Research, 2019, 8
ISSN
2046-1402
Publisher
F1000 Research Ltd
Journal / Book Title
F1000Research
Volume
8
Copyright Statement
© 2019 Hamilton C and Anand PK. This is an open access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor
Wellcome Trust
Medical Research Council (MRC)
Grant Number
108248/Z/15/Z
MR/S00968X/1
Subjects
Golgi
IL-18
IL-1β
NLRP3
SREBP2
caspase-1
cholesterol
endoplasmic reticulum
inflammasome
mitochondria
Publication Status
Published online
Date Publish Online
2019-05-17