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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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Regulation of Nuclear Protein Sorting01:45

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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 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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Directionality of Nuclear Transport01:42

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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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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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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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Single-Molecule Imaging of Nuclear Transport
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Los poros nucleares se dilatan y se contraen en el celuloide

Christian E Zimmerli1,2,3, Matteo Allegretti1,3, Vasileios Rantos4,5

  • 1Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.

Science (New York, N.Y.)
|November 11, 2021
PubMed
Resumen

Los complejos de poros nucleares (NPC) cambian de tamaño dinámicamente. En las células en crecimiento, las NPC se dilatan, pero se contraen bajo estrés, revelando un vínculo entre la tensión de la envoltura nuclear y la conformación de las NPC.

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Área de la Ciencia:

  • Biología celular
  • Biología estructural
  • La biofísica

Sus antecedentes:

  • Los complejos de poros nucleares (NPC) son cruciales para el transporte nucleocitoplasmático en las células eucariotas.
  • Las NPC forman una estructura cilíndrica de ~30 nucleoporinas, que regulan el tráfico molecular entre el núcleo y el citoplasma.
  • La naturaleza dinámica y las variaciones conformacionales de los NPC no se comprenden completamente.

Objetivo del estudio:

  • Investigar los cambios conformacionales a gran escala de las NPC en células vivas.
  • Aclarar los mecanismos moleculares y las condiciones fisiológicas que rigen las variaciones de tamaño de las NPC.
  • Establecer un vínculo entre la tensión de la membrana de la envoltura nuclear y la estructura del NPC.

Principales métodos:

  • Se empleó la tomografía criolectrónica para visualizar los NPC in situ.
  • Se utilizó el modelado estructural integrador para reconstruir las conformaciones de NPC.
  • Se aplicaron condiciones celulares como el crecimiento exponencial, el agotamiento de la energía y el estrés osmótico.

Principales resultados:

  • Los NPC en células de crecimiento exponencial exhibieron una conformación dilatada.
  • Los NPC se contraen de manera reversible en condiciones de agotamiento de la energía celular y estrés osmótico hipertónico.
  • Estos hallazgos sugieren que la conformación de NPC es sensible a los estados fisiológicos celulares.

Conclusiones:

  • El estudio revela que el diámetro de NPC no es estático y varía con las condiciones celulares.
  • Se propone un modelo en el que la tensión de la membrana de la envoltura nuclear influye en la conformación del NPC.
  • Esto proporciona nuevos conocimientos sobre la regulación dinámica del transporte nucleocitoplasmático.