The Microtubule-associated Protein EB1 Links AIM2 Inflammasomes with Autophagy-dependent Secretion

Wang, Lijie; Huang, Hsin‐Yi; Huang, Meng-Pin; Liou, Willisa; Chang, Ya‐Ting; Wu, Chih‐Ching; Ojcius, David M.; Chang, Yu‐Sun

doi:10.1074/jbc.m114.559153

Cited by 48 publications

(34 citation statements)

References 39 publications

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“…Recently, the secretion of IL-1β has been linked to the autophagy machinery [1, 3, 14]. These studies have been extended and expanded by several groups [19, 20, 25, 26]. This was made possible in part by the details of autophagy-assisted unconventional secretion uncovered in yeast through the power of genetics [12, 13].…”

Section: Secretory Autophagy As a Form Of Unconventional Protein Secrmentioning

confidence: 99%

“…This was made possible in part by the details of autophagy-assisted unconventional secretion uncovered in yeast through the power of genetics [12, 13]. The yeast studies, although recently re-interpreted by one of the groups [27], have paved the way for reports on autophagic secretion in mammalian cells of a number of cytosolic proteins [3, 14, 19, 20, 25, 26], in keeping with the earlier definition of a large repertoire secretome induced by starvation [28], a classical signal for induction of autophagy.…”

Section: Secretory Autophagy As a Form Of Unconventional Protein Secrmentioning

confidence: 99%

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Secretory autophagy

Ponpuak

Mandell

Kimura

et al. 2015

Current Opinion in Cell Biology

409

356

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Autophagy, once viewed exclusively as a cytoplasmic auto-digestive process, has its less intuitive but biologically distinct non-degradative roles. One manifestation of these functions of the autophagic machinery is the process termed secretory autophagy. Secretory autophagy facilitates unconventional secretion of the cytosolic cargo such as leaderless cytosolic proteins, which unlike proteins endowed with the leader (N-terminal signal) peptides cannot enter the conventional secretory pathway normally operating via the endoplasmic reticulum and the Golgi apparatus. Secretory autophagy may also export more complex cytoplasmic cargo and help excrete particulate substrates. Autophagic machinery and autophagy as a process also affect conventional secretory pathways, including the constitutive and regulated secretion, as well as promote alternative routes for trafficking of integral membrane proteins to the plasma membrane. Thus, autophagy and autophagic factors are intimately intertwined at many levels with secretion and polarized sorting in eukaryotic cells.

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Section: Secretory Autophagy As a Form Of Unconventional Protein Secrmentioning

confidence: 99%

Section: Secretory Autophagy As a Form Of Unconventional Protein Secrmentioning

confidence: 99%

Secretory autophagy

Ponpuak

Mandell

Kimura

et al. 2015

Current Opinion in Cell Biology

409

356

View full text Add to dashboard Cite

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“…The autophagosome has been proposed to promote the release of cytokines activated by caspase-1, thereby positively cooperating with the inflammasome. For example, recruitment of the autophagy machinery by the activated AIM2 inflammasome has been proposed to mediate the release of IL-1β via exocytosis of the autophagosome [32]. Thus, IL-1β can be released in an autophagy-dependent manner that requires SNAREs and syntaxins [33].…”

Section: Crosstalk Between Autophagy and The Inflammasome Machineriesmentioning

confidence: 99%

Checks and Balances between Autophagy and Inflammasomes during Infection

Seveau

Turner

Gavrilin

et al. 2018

Journal of Molecular Biology

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Autophagy and inflammasome complex assembly are physiological processes that control homeostasis, inflammation, and immunity. Autophagy is a ubiquitous pathway that degrades cytosolic macromolecules or organelles, as well as intracellular pathogens. Inflammasomes are multi-protein complexes that assemble in the cytosol of cells upon detection of pathogen- or danger-associated molecular patterns. A critical outcome of inflammasome assembly is the activation of the serine protease caspase-1, which activates the pro-inflammatory cytokine precursors pro-IL-1β and pro-IL-18. Studies on chronic inflammatory diseases, heart diseases, Alzheimer's disease, and multiple sclerosis revealed that autophagy and inflammasomes intersect and regulate each other. In the context of infectious diseases, however, less is known about the interplay between autophagy and inflammasome assembly, although it is becoming evident that pathogens have evolved multiple strategies to inhibit and/or subvert these pathways and to take advantage of their intricate crosstalk. An improved appreciation of these pathways and their subversion by diverse pathogens is expected to help in the design of anti-infective therapeutic interventions.

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“…This pathway therefore contributes to autophagy-mediated reduction in IL-1β secretion in response to NLRP3 inducers (38). However, two other studies suggest that autophagy is actually required for the unconventional secretion of IL-1β, and reducing autophagy can lead to reduced IL-1β release in response to AIM2 and NLRP3 activators in macrophages (39,40). In one of the studies, Wang et al showed that autophagy-dependent secretion of IL-1β after AIM2 inflammasome activation required microtubuleassociated protein end-binding protein 1 (39).…”

Section: Multifaceted Roles For Autophagymentioning

confidence: 99%

“…However, two other studies suggest that autophagy is actually required for the unconventional secretion of IL-1β, and reducing autophagy can lead to reduced IL-1β release in response to AIM2 and NLRP3 activators in macrophages (39,40). In one of the studies, Wang et al showed that autophagy-dependent secretion of IL-1β after AIM2 inflammasome activation required microtubuleassociated protein end-binding protein 1 (39). Disruption of autophagy by inhibition of AMPK activity was able to block poly(dA:dT)-induced AIM2-mediated IL-1β secretion (39).…”

Section: Multifaceted Roles For Autophagymentioning

confidence: 99%

Inflammasome and Autophagy Regulation: A Two-way Street

Sun

Fan

Billiar

et al. 2017

Mol Med

162

133

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Inflammation plays a significant role in protecting hosts against pathogens. Inflammation induced by noninfectious endogenous agents can be detrimental and, if excessive, can result in organ and tissue damage. The inflammasome is a major innate immune pathway that can be activated via both exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Inflammasome activation involves formation and oligomerization of a protein complex including a nucleotide oligomerization domain (NOD)-like receptor (NLR), an adaptor protein and pro-caspase-1. This then allows cleavage and activation of caspase-1, followed by downstream cleavage and release of proinflammatory cytokines interleukin (IL)-1β and IL-18 from innate immune cells. Hyperinflammation caused by unrestrained inflammasome activation is linked with multiple inflammatory diseases, including inflammatory bowel disease, Alzheimer's disease and multiple sclerosis. So there is an understandable rush to understand mechanisms that regulate such potent inflammatory pathways. Autophagy has now been identified as a main regulator of inflammasomes. Autophagy is a vital intracellular process involved in cellular homeostasis, recycling and removal of damaged organelles (eg, mitochondria) and intracellular pathogens. Autophagy is regulated by proteins that are important in endosomal/phagosomal pathways, as well as by specific autophagy proteins coded for by autophagy-related genes. Cytosolic components are surrounded and contained by a double-membraned vesicle, which then fuses with lysosomes to enable degradation of the contents. Autophagic removal of intracellular DAMPs, inflammasome components or cytokines can reduce inflammasome activation. Similarly, inflammasomes can regulate the autophagic process, allowing for a two-way mutual regulation of inflammation that may hold the key for treatment of multiple diseases.

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The Microtubule-associated Protein EB1 Links AIM2 Inflammasomes with Autophagy-dependent Secretion

Cited by 48 publications

References 39 publications

Secretory autophagy

Secretory autophagy

Checks and Balances between Autophagy and Inflammasomes during Infection

Inflammasome and Autophagy Regulation: A Two-way Street

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