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相关概念视频

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 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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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 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.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
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Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

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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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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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相关实验视频

Updated: Jun 14, 2025

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells
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C9orf72 聚PR 与核孔复合体的相互作用

Hamidreza Jafarinia1, Erik Van der Giessen1, Patrick R Onck1

  • 1Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands.

Biophysical journal
|August 29, 2024
PubMed
概括
此摘要是机器生成的。

在ALS/FTD中有毒的聚烯-阿基因 (PR) 不会在核孔复合体 (NPC) 中聚合. 相反,PR通过NPC转移,转移难度随着PR长度的增加而增加.

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Genome-wide Protein-protein Interaction Screening by Protein-fragment Complementation Assay PCA in Living Cells
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科学领域:

  • 神经科学是一个神经科学.
  • 分子生物学分子生物学
  • 生物物理学的生物物理.

背景情况:

  • C9orf72基因突变是肌缩性侧面硬化/前性痴呆 (ALS/FTD) 的主要原因.
  • 这种突变产生有毒的二重复蛋白质,包括涉及到细胞功能障碍的多--氨酸 (polyPR).
  • 假设PolyPR通过干扰核孔综合体 (NPC) 来破坏核细胞质体运输 (NCT).

研究的目的:

  • 研究聚PR与NPC相互作用的分子机制.
  • 阐明聚PR如何影响核细胞质运输 (NCT).
  • 了解NPC在聚PR介导细胞缺陷中的作用.

主要方法:

  • 使用粗粒度的分子动力学模拟.
  • 使用了polyPR和酵母NPC的模型,包括FG-核波林 (FG-Nups).
  • 在NPC中分析了polyPR的相互作用和转位途径.

主要成果:

  • 聚PR不会在NPC中聚合,也不会永久地与FG-Nups结合.
  • 聚PR通过NPC的中部低密度区域转移.
  • 转移面临更高的能源障碍和更长的聚PR链的更窄的道.
  • 在polyPR和FG-Nups之间,绝缘相互作用占主导地位,其他力量的贡献较小.

结论:

  • 聚PR穿过NPC,而不是在NPC中积累.
  • 聚烯的尺寸会影响其转移效率和能源需求.
  • 这些发现为ALS/FTD中聚PR诱导的NCT中断的分子基础提供了洞察力.