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Related Concept Videos

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 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.
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Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
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Nuclear Export01:42

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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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The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
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The ER, Golgi apparatus, endosomes, and lysosomes work in tandem to modify, sort, and package proteins and lipids. An integrated membrane trafficking network facilitates the back and forth shuttling of molecules within different organelles in the same cell or across the cell membrane.
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Single-Molecule Imaging of Nuclear Transport
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Extracellular membrane particles en route to the nucleus - exploring the VOR complex.

Aurelio Lorico1, Mark F Santos1, Jana Karbanová2,3

  • 1Department of Basic Sciences, College of Osteopathic Medicine, Touro University Nevada, Henderson, NV 89014, U.S.A.

Biochemical Society Transactions
|May 14, 2025
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Summary

Extracellular vesicles (EVs) communicate between cells, but how they work inside is unclear. We found EVs can deliver cargo to the cell nucleus via a novel pathway, offering new therapeutic targets for diseases like cancer.

Keywords:
HIV-1VOR complexcancerextracellular vesiclesnucleoplasmic reticulumspathasome

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Intercellular communication is vital for multicellular organisms.
  • Extracellular vesicles (EVs) are key mediators of this communication.
  • While EV release and uptake are understood, their intracellular actions remain largely unknown.

Purpose of the Study:

  • To investigate the intracellular fate and mechanisms of extracellular vesicles (EVs) after cellular uptake.
  • To identify novel pathways for EV cargo delivery within cells.
  • To explore potential clinical applications targeting EV pathways.

Main Methods:

  • Focus on EV heterogeneity, release, and uptake pathways.
  • Investigated a novel intracellular pathway for EV cargo nuclear transfer.
  • Utilized the VOR (VAP-A-ORP3-Rab7) complex for late endosome docking to the nuclear membrane.

Main Results:

  • A fraction of endocytosed EVs reaches the nuclear compartment.
  • The VOR complex mediates docking of late endosomes to the outer nuclear membrane.
  • EV cargoes are transferred into the nucleoplasm via nuclear pores.

Conclusions:

  • A novel pathway facilitates the nuclear transfer of EV cargoes.
  • This pathway involves the VOR complex and nuclear pore translocation.
  • Targeting this pathway could offer new therapeutic strategies for EV-implicated diseases.