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Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Nuclear Protein Sorting01:34

Nuclear Protein Sorting

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Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
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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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Nuclear Export01:42

Nuclear Export

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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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GPCR Desensitization01:12

GPCR Desensitization

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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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Nuclear cGAS: sequestration and beyond.

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|August 10, 2021
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Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a DNA sensor involved in immunity. Emerging research highlights its nuclear functions beyond innate immunity, suggesting novel roles in regulating cell nuclear processes.

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Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic sensor for double-stranded DNA.
  • cGAS activates type I interferon and inflammatory responses through the STING pathway.
  • Recent studies show cGAS localizes to nuclear substructures, including nucleosomes and replication forks.

Purpose of the Study:

  • To review the current understanding of nuclear cGAS.
  • To explore the non-canonical nuclear functions of cGAS.
  • To identify open questions regarding cGAS's novel roles and mechanisms in the nucleus.

Main Methods:

  • Literature review of existing studies on cGAS localization and function.
  • Analysis of evidence for cGAS association with nuclear substructures.
  • Synthesis of current knowledge on cGAS's dual role in innate immunity and nuclear processes.

Main Results:

  • cGAS is found in the nucleus associated with DNA replication forks, double-strand breaks, and centromeres.
  • While its innate immune role is established, nuclear functions are less understood.
  • Evidence suggests cGAS has roles beyond dsDNA sensing in the nucleus.

Conclusions:

  • Nuclear cGAS has functions distinct from its established role in innate immunity.
  • Further research is needed to elucidate the novel roles and mechanisms of nuclear cGAS.
  • cGAS may act as a key regulator of cell nuclear functions.