Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Channelling inflammation: gasdermins in physiology and disease.

ABSTRACT: Gasdermins were recently identified as the mediators of pyroptosis - inflammatory cell death triggered by cytosolic sensing of invasive infection and danger signals. Upon activation, gasdermins form cell membrane pores, which release pro-inflammatory cytokines and alarmins and damage the integrity of the cell membrane. Roles for gasdermins in autoimmune and inflammatory diseases, infectious diseases, deafness and cancer are emerging, revealing potential novel therapeutic avenues. Here, we review current knowledge of the family of gasdermins, focusing on their mechanisms of action and roles in normal physiology and disease. Efforts to develop drugs to modulate gasdermin activity to reduce inflammation or activate more potent immune responses are highlighted.

SUBMITTER: Liu X

PROVIDER: S-EPMC7944254 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Channelling inflammation: gasdermins in physiology and disease.

Liu Xing X Xia Shiyu S Zhang Zhibin Z Wu Hao H Lieberman Judy J

Nature reviews. Drug discovery 20210310 5

Gasdermins were recently identified as the mediators of pyroptosis - inflammatory cell death triggered by cytosolic sensing of invasive infection and danger signals. Upon activation, gasdermins form cell membrane pores, which release pro-inflammatory cytokines and alarmins and damage the integrity of the cell membrane. Roles for gasdermins in autoimmune and inflammatory diseases, infectious diseases, deafness and cancer are emerging, revealing potential novel therapeutic avenues. Here, we review ...[more]

PMID: 33692549

Similar Datasets

Gasdermins and their role in immunity and inflammation.

Project description:The gasdermins are a family of pore-forming proteins recently implicated in the immune response. One of these proteins, gasdermin D (GSDMD), has been identified as the executioner of pyroptosis, an inflammatory form of lytic cell death that is induced upon formation of caspase-1-activating inflammasomes. The related proteins GSDME and GSDMA have also been implicated in autoimmune diseases and certain cancers. Most gasdermin proteins are believed to have pore-forming capabilities. The best-studied member, GSDMD, controls the release of the proinflammatory cytokines IL-1ß and IL-18 and pyroptotic cell death. Because of its potential as a driver of inflammation in septic shock and autoimmune diseases, GSDMD represents an attractive drug target. In this review, we discuss the gasdermin proteins with particular emphasis on GSDMD and its mechanism of action and biological significance.

| S-EPMC6829603 | biostudies-literature

Intestinal Gasdermins for regulation of inflammation and tumorigenesis.

Project description:Gasdermins (GSDMs) protein family express in intestinal epithelial cells or lamina propria immune cells, and play a nonnegligible function during gut homeostasis. With the gradually in-depth investigation of GSDMs protein family, the proteases that cleave GSDMA-E have been identified. Intestinal GSDMs-induced pyroptosis is demonstrated to play a crucial role in the removal of self-danger molecules and clearance of pathogenic organism infection by mediating inflammatory reaction and collapsing the protective niche for pathogens. Simultaneously, excessive pyroptosis leading to the release of cellular contents including inflammatory mediators into the extracellular environment, enhancing the mucosal immune response. GSDMs-driver pyroptosis also participates in a novel inflammatory cell death, PANoptosis, which makes a significant sense to the initiation and progression of gut diseases. Moreover, GSDMs are expressed in healthy intestinal tissue without obvious pyroptosis and inflammation, indicating the potential intrinsic physiological functions of GSDMs that independent of pyroptotic cell death during maintenance of intestinal homeostasis. This review provides an overview of the latest advances in the physiological and pathological properties of GSDMs, including its mediated pyroptosis, related PANoptosis, and inherent functions independent of pyroptosis, with a focus on their roles involved in intestinal inflammation and tumorigenesis.

| S-EPMC9732009 | biostudies-literature

Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease.

Project description:Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the increasing severity of infections. The activity of GSDMs requires meticulous regulation. The dynamic modulation of GSDMs involves many aspects, including autoinhibitory structures, proteolytic cleavage, lipid binding and membrane translocation (oligomerization and pre-pore formation), oligomerization (pore formation) and pore removal for membrane repair. As the most comprehensive and efficient regulatory pathway, posttranslational modifications (PTMs) are widely implicated in the regulation of these aspects. In this comprehensive review, we delve into the complex mechanisms through which a variety of proteases cleave GSDMs to enhance or hinder their function. Moreover, we summarize the intricate regulatory mechanisms of PTMs that govern GSDMs-induced pyroptosis.

| S-EPMC10539709 | biostudies-literature

RNA channelling by the archaeal exosome.

Project description:Exosomes are complexes containing 3' --> 5' exoribonucleases that have important roles in processing, decay and quality control of various RNA molecules. Archaeal exosomes consist of a hexameric core of three active RNase PH subunits (ribosomal RNA processing factor (Rrp)41) and three inactive RNase PH subunits (Rrp42). A trimeric ring of subunits with putative RNA-binding domains (Rrp4/cep1 synthetic lethality (Csl)4) is positioned on top of the hexamer on the opposite side to the RNA degrading sites. Here, we present the 1.6 A resolution crystal structure of the nine-subunit exosome of Sulfolobus solfataricus and the 2.3 A structure of this complex bound to an RNA substrate designed to be partly trimmed rather than completely degraded. The RNA binds both at the active site on one side of the molecule and on the opposite side in the narrowest constriction of the central channel. Multiple substrate-binding sites and the entrapment of the substrate in the central channel provide a rationale for the processive degradation of extended RNAs and the stalling of structured RNAs.

| S-EPMC1866195 | biostudies-literature

Channelling protons out of the heart.

Project description: Not available

| S-EPMC9322403 | biostudies-literature

Modulation of Autoimmune and Autoinflammatory Diseases by Gasdermins.

Project description:Autoimmune diseases and autoinflammatory diseases are two types of the immune system disorders. Pyroptosis, a highly inflammatory cell death, plays an important role in diseases of immune system. The gasdermins belong to a pore-forming protein gene family which are mainly expressed in immune cells, gastrointestinal tract, and skin. Gasdermins are regarded as an executor of pyroptosis and have been shown to possess various cellular functions and pathological effects such as pro-inflammatory, immune activation, mediation of tumor, etc. Except for infectious diseases, the vital role of gasdermins in autoimmune diseases, autoinflammatory diseases, and immune-related neoplastic diseases has been proved recently. Therefore, gasdermins have been served as a potential therapeutic target for immune disordered diseases. The review summarizes the basic molecular structure and biological function of gasdermins, mainly discusses their role in autoimmune and autoinflammatory diseases, and highlights the recent research on gasdermin family inhibitors so as to provide potential therapeutic prospects.

| S-EPMC9199384 | biostudies-literature

Passing the Baton: Substrate Channelling in Respiratory Metabolism.

Project description:Despite species-specific differences in the pathways of respiratory metabolism are remarkably conserved across the kingdoms of life with glycolysis, the tricarboxylic acid cycle, and mitochondrial electron transport chain representing the major components of the process in the vast majority of organisms. In addition to being of critical importance in fueling life itself these pathways serve as interesting case studies for substrate channelling with research on this theme having been carried out for over 40 years. Here we provide a cross-kingdom review of the ample evidence for protein-protein interaction and enzyme assemblies within the three component pathways as well as describing the scarcer available evidence for substrate channelling itself.

| S-EPMC6750097 | biostudies-literature

Channelling and formation of 'active' formaldehyde in dimethylglycine oxidase.

Project description:Here we report crystal structures of dimethylglycine oxidase (DMGO) from the bacterium Arthrobacter globiformis, a bifunctional enzyme that catalyzes the oxidation of N,N-dimethyl glycine and the formation of 5,10-methylene tetrahydrofolate. The N-terminal region binds FAD covalently and oxidizes dimethylglycine to a labile iminium intermediate. The C-terminal region binds tetrahydrofolate, comprises three domains arranged in a ring-like structure and is related to the T-protein of the glycine cleavage system. The complex with folinic acid indicates that this enzyme selectively activates the N10 amino group for initial attack on the substrate. Dead-end reactions with oxidized folate are avoided by the strict stereochemical constraints imposed by the folate-binding funnel. The active sites in DMGO are approximately 40 A apart, connected by a large irregular internal cavity. The tetrahydrofolate-binding funnel serves as a transient entry-exit port, and access to the internal cavity is controlled kinetically by tetrahydrofolate binding. The internal cavity enables sequestration of the reactive iminium intermediate prior to reaction with tetrahydrofolate and avoids formation of toxic formaldehyde. This mode of channelling in DMGO is distinct from other channelling mechanisms.

| S-EPMC175785 | biostudies-literature

WNT5B in Physiology and Disease.

Project description:WNT5B, a member of the WNT family of proteins that is closely related to WNT5A, is required for cell migration, cell proliferation, or cell differentiation in many cell types. WNT5B signals through the non-canonical β-catenin-independent signaling pathway and often functions as an antagonist of canonical WNT signaling. Although WNT5B has a high amino acid identity with WNT5A and is often assumed to have similar activities, WNT5B often exhibits unique expression patterns and functions. Here, we describe the distinct effects and mechanisms of WNT5B on development, bone, adipose tissue, cardiac tissue, the nervous system, the mammary gland, the lung and hematopoietic cells, compared to WNT5A. We also highlight aberrances in non-canonical WNT5B signaling contributing to diseases such as osteoarthritis, osteoporosis, obesity, type 2 diabetes mellitus, neuropathology, and chronic diseases associated with aging, as well as various cancers.

| S-EPMC8129536 | biostudies-literature

Multiple channelling single-photon emission with scattering holography designed metasurfaces.

Project description:Channelling single-photon emission in multiple well-defined directions and simultaneously controlling its polarization characteristics is highly desirable for numerous quantum technology applications. We show that this can be achieved by using quantum emitters (QEs) nonradiatively coupled to surface plasmon polaritons (SPPs), which are scattered into outgoing free-propagating waves by appropriately designed metasurfaces. The QE-coupled metasurface design is based on the scattering holography approach with radially diverging SPPs as reference waves. Using holographic metasurfaces fabricated around nanodiamonds with single Ge vacancy centres, we experimentally demonstrate on-chip integrated efficient generation of two well-collimated single-photon beams propagating along different 15° off-normal directions with orthogonal linear polarizations.

| S-EPMC10558519 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data