Extended subsite profiling of the pyroptosis effector protein gasdermin D reveals a region recognized by inflammatory caspase-11

Bibo-Verdugo, Betsaida; Snipas, Scott J.; Kołt, Sonia; Poręba, Marcin; Salvesen, Guy S.

doi:10.1074/jbc.ra120.014259

Cited by 41 publications

(38 citation statements)

References 58 publications

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“…When activated, reminiscent of caspase-1, the noncanonical inflammasome caspases convert GSDMD into GSDMD-N to induce pyroptosis. In contrast to caspase-1, caspase-11 is not able to process pro-IL-1b and pro-IL-18, while caspase-4 may process pro-IL-18 but not pro-IL-1b, and caspase-5 possesses a weak ability to process pro-IL-1b and pro-IL-18 (24,77,78). These results suggest that noncanonical inflammasomes play a more important role in the induction of pyroptosis than in the direct maturation of IL-1b and IL-18.…”

Section: Structure and Activation Of Inflammasomesmentioning

confidence: 99%

Inflammasomes in Alveolar Bone Loss

2021

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Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast–osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.

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Section: Structure and Activation Of Inflammasomesmentioning

confidence: 99%

Inflammasomes in Alveolar Bone Loss

2021

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“…This is in line with reports showing that caspase-1 activation in Gsdmd -deficient mouse macrophages engages rapid apoptosis via Bid cleavage 14–16 . Of note, while mouse caspase-11 is apparently not able to induce this type of apoptosis 7–9 , we found that optoCaspase-4 and −5 caused GSDMD-independent apoptosis, which could possibly be due to their wider substrate profile 17 . OptoCaspase activation efficiently induced pyroptosis in commonly used laboratory cell lines, such as MCF7 cells, HeLa, Caco-2, HT-29 and HaCaT, ( Fig.…”

Section: Resultsmentioning

confidence: 58%

Optogenetic activators of apoptosis, necroptosis and pyroptosis for probing cell death dynamics and bystander cell responses

Shkarina

Carvalho

Santos

et al. 2021

Preprint

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Targeted and specific induction of cell death in individual or groups of cells holds the potential for new insights into the response of tissues or organisms to different forms of death. Here we report the development of optogenetically-controlled cell death effectors (optoCDEs), a novel class of optogenetic tools that enables light-mediated induction of three types of programmed cell death (PCD), apoptosis, pyroptosis and necroptosis, using Arabidopsis thaliana photosensitive protein Cryptochrome2. OptoCDEs enable rapid and highly specific induction of PCD in human, mouse and zebrafish cells and are suitable for a wide range of applications, such as sub-lethal cell death induction or precise elimination of single cells or cell populations in vitro and in vivo. As the proof-of-concept, we utilize optoCDEs to assess the differences in the neighboring cell response to apoptotic or necrotic PCD, revealing a new role for shingosine-1-phosphate signaling in regulating the efferocytosis of apoptotic cell by epithelia.

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“…as their catalytic domain is most similar to that found in hCasp-4, a caspase that has no considerable ICE activity (Bibo-Verdugo et al, 2020;Faucheu et al, 1995). The presence of .…”

Section: Evolutionary Symmetry Between the Mechanisms Of Casp-1-like mentioning

confidence: 84%

Evolution-inspired dissection of caspase activities enables the redesign of caspase-4 into an LPS sensing interleukin-1 converting enzyme

Devant

Cao

Kagan

2020

Preprint

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Innate immune signaling pathways comprise multiple proteins that promote inflammation. This multistep means of information transfer suggests that complexity is a prerequisite for pathway design. Herein, we examined this possibility by studying caspases that regulate inflammasome-dependent inflammation. Several caspases differ in their ability to recognize bacterial LPS and cleave interleukin-1β (IL-1β). No caspase is known to contain both activities, yet distinct caspases with complementary activities bookend an LPS-induced pathway to IL-1β cleavage. Using unique caspases present in carnivorans as a guide, we identified molecular determinants of IL-1β cleavage specificity within caspase-1. This knowledge enabled the redesign of human caspase-4 to operate as a one-protein signaling pathway, which intrinsically links LPS detection to IL-1β cleavage and release, independent of inflammasomes. Strikingly, cat caspase-4 displays the activities of redesigned human caspase-4. These findings illustrate natural signaling pathway diversity and highlight how multistep innate immune pathways can be condensed into a single protein.

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Extended subsite profiling of the pyroptosis effector protein gasdermin D reveals a region recognized by inflammatory caspase-11

Cited by 41 publications

References 58 publications

Inflammasomes in Alveolar Bone Loss

Inflammasomes in Alveolar Bone Loss

Optogenetic activators of apoptosis, necroptosis and pyroptosis for probing cell death dynamics and bystander cell responses

Evolution-inspired dissection of caspase activities enables the redesign of caspase-4 into an LPS sensing interleukin-1 converting enzyme

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