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Related Concept Videos

Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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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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Nuclear Localization Signals and Import01:46

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Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
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GTPases and their Regulation02:14

GTPases and their Regulation

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Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
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cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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Directionality of Nuclear Transport01:42

Directionality of Nuclear Transport

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Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of  Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
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Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
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Related Experiment Video

Updated: Jun 30, 2025

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins
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cGAS: action in the nucleus.

Yikai Lu1, Mengmeng Zhao2, Li Chen1

  • 1Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

Frontiers in Immunology
|March 22, 2024
PubMed
Summary
This summary is machine-generated.

Cyclic GMP-AMP synthase (cGAS) is a key immune sensor. Recent research reveals its nuclear functions in DNA repair and replication, alongside nucleo-cytoplasmic transport mechanisms.

Keywords:
activationcyclic GMP-AMP synthase (cGAS)functionslocalizationnucleusstructure

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Cyclic GMP-AMP synthase (cGAS) is a critical cytoplasmic DNA sensor involved in innate immunity.
  • Emerging evidence highlights cGAS's presence and novel functions within the nucleus.
  • These nuclear roles include regulating DNA repair, nuclear membrane integrity, chromosome stability, and angiogenesis.

Purpose of the Study:

  • To review the mechanisms of nucleo-cytoplasmic transport of cGAS.
  • To summarize the regulation of cGAS activity in the nucleus.
  • To explore the non-canonical functions of nuclear cGAS and its clinical potential.

Main Methods:

  • Literature review of recent studies on cGAS structure, localization, and function.
  • Analysis of research detailing cGAS nucleo-cytoplasmic transport mechanisms.
  • Synthesis of findings on cGAS activity regulation and non-canonical nuclear roles.

Main Results:

  • cGAS exhibits significant non-canonical functions within the nucleus, extending beyond its innate immune role.
  • Mechanisms governing cGAS transport between the cytoplasm and nucleus are increasingly understood.
  • Regulation of cGAS activation and its diverse nuclear activities are key areas of recent discovery.

Conclusions:

  • Nuclear cGAS possesses critical, non-canonical functions in processes like DNA repair and replication.
  • Understanding cGAS nucleo-cytoplasmic transport and nuclear activity regulation is vital.
  • Further research into nuclear cGAS holds promise for novel therapeutic strategies and clinical translation.