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Related Concept Videos

Activation and Inactivation of G Proteins01:22

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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Intracellular Signaling Cascades01:24

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Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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Calmodulin-dependent Signaling01:16

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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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Amplifying Signals via Enzymatic Cascade01:22

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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IP3/DAG Signaling Pathway

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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cGAS-STING signaling.

Zhiqi Sun1, Veit Hornung1

  • 1Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany; Max-Planck Institute of Biochemistry, Martinsried, Germany.

Current Biology : CB
|July 12, 2022
PubMed
Summary
This summary is machine-generated.

The cGAS-STING pathway detects foreign DNA to trigger immune responses, producing antiviral interferons. Aberrant activation by self-DNA causes inflammation and disease.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway is a key vertebrate system for sensing foreign DNA.
  • This pathway initiates innate immune responses, including the production of type I interferons and interferon-stimulated genes (ISGs) with antiviral functions.

Purpose of the Study:

  • To introduce the fundamental principles of the cGAS-STING signaling pathway in vertebrates.
  • To highlight recent discoveries linking cGAS-STING signaling to human diseases and cellular processes.

Main Methods:

  • Review of existing literature on cGAS-STING pathway function.
  • Analysis of recent studies on the role of cGAS-STING in disease pathogenesis.

Main Results:

  • The cGAS-STING pathway's role in sensing double-stranded DNA (dsDNA) and synthesizing cyclic GMP-AMP (cGAMP).
  • cGAMP acts as a second messenger, activating STING and downstream immune signaling.
  • Aberrant activation by host DNA can result in sterile inflammation, tissue damage, and premature aging.

Conclusions:

  • The cGAS-STING pathway is crucial for antiviral defense and has ancient evolutionary origins.
  • Dysregulation of this pathway contributes to various human diseases, underscoring its clinical relevance.