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Publication Detail
Selectivity mechanism of the nuclear pore complex characterized by single cargo tracking
  • Publication Type:
    Journal article
  • Publication Sub Type:
    JOUR
  • Authors:
    Lowe AR, Siegel JJ, Kalab P, Siu M, Weis K, Liphardt JT
  • Publication date:
    2010
  • Pagination:
    600, 603
  • Journal:
    Nature
  • Volume:
    467
  • Medium:
    7315
  • Print ISSN:
    1476-4687
  • Keywords:
    Active Transport, Cell Nucleus Cytoplasm/metabolism Diffusion HeLa Cells Humans Molecular Weight Movement Nuclear Pore/ metabolism Nucleocytoplasmic Transport Proteins/ metabolism Protein Transport Proteins/chemistry/metabolism Quantum Dots Substrate Specificity ran GTP-Binding Protein/metabolism
  • Notes:
    Lowe, Alan R Siegel, Jake J Kalab, Petr Siu, Merek Weis, Karsten Liphardt, Jan T GM058065/GM/NIGMS NIH HHS/United States GM77856/GM/NIGMS NIH HHS/United States R01 GM058065-13/GM/NIGMS NIH HHS/United States R01 GM077856-04/GM/NIGMS NIH HHS/United States R01 GM084716-02/GM/NIGMS NIH HHS/United States U54 CA143836-01/CA/NCI NIH HHS/United States U54CA143836/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Nature NIHMS213887 nature09285 [pii] Nature. 2010 Sep 30;467(7315):600-3. doi: 10.1038/nature09285. Epub 2010 Sep 1. The nuclear pore complex (NPC) mediates all exchange between the cytoplasm and the nucleus. Small molecules can passively diffuse through the NPC, whereas larger cargos require transport receptors to translocate. How the NPC facilitates the translocation of transport receptor/cargo complexes remains unclear. To investigate this process, we tracked single protein-functionalized quantum dot cargos as they moved through human NPCs. Here we show that import proceeds by successive substeps comprising cargo capture, filtering and translocation, and release into the nucleus. Most quantum dots are rejected at one of these steps and return to the cytoplasm, including very large cargos that abort at a size-selective barrier. Cargo movement in the central channel is subdiffusive and cargos that can bind more transport receptors diffuse more freely. Without Ran GTPase, a critical regulator of transport directionality, cargos still explore the entire NPC, but have a markedly reduced probability of exit into the nucleus, suggesting that NPC entry and exit steps are not equivalent and that the pore is functionally asymmetric to importing cargos. The overall selectivity of the NPC seems to arise from the cumulative action of multiple reversible substeps and a final irreversible exit step.
Abstract
The nuclear pore complex (NPC) mediates all exchange between the cytoplasm and the nucleus. Small molecules can passively diffuse through the NPC, whereas larger cargos require transport receptors to translocate. How the NPC facilitates the translocation of transport receptor/cargo complexes remains unclear. To investigate this process, we tracked single protein-functionalized quantum dot cargos as they moved through human NPCs. Here we show that import proceeds by successive substeps comprising cargo capture, filtering and translocation, and release into the nucleus. Most quantum dots are rejected at one of these steps and return to the cytoplasm, including very large cargos that abort at a size-selective barrier. Cargo movement in the central channel is subdiffusive and cargos that can bind more transport receptors diffuse more freely. Without Ran GTPase, a critical regulator of transport directionality, cargos still explore the entire NPC, but have a markedly reduced probability of exit into the nucleus, suggesting that NPC entry and exit steps are not equivalent and that the pore is functionally asymmetric to importing cargos. The overall selectivity of the NPC seems to arise from the cumulative action of multiple reversible substeps and a final irreversible exit step.
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