Nuclear transport facilitated by the interaction between nuclear pores and carbohydrates

Sekiguchi, Shota; Niikura, Kenichi; Matsuo, Yasutaka; Yoshimura, Shige H.; Ijiro, Kuniharu

doi:10.1039/c1ra00616a

Cited by 4 publications

(3 citation statements)

References 44 publications

(48 reference statements)

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“…Interestingly, the implication of our model is supported by the NLS-independent nuclear import of glycosylated substances as explored for gene therapy and nanomedicine. Remarkably, BSA, plasmid DNA, , and CdTe/ZnS quantum dots with Stokes radii of up to 6.1 nm were glycosylated to be imported efficiently into the nuclei of living cells. We argue that the nuclear import of glycosylated substances is somehow mediated through the peripheral route because it is prevented by WGA …”

Section: Results and Discussionmentioning

confidence: 99%

“…Moreover, our model implies that the peripheral route should be targeted for the efficient nuclear import of macromolecular and nanomaterial therapeutics. The efficient nuclear import of glycosylated plasmids , and nanoparticles has been demonstrated for gene therapy and nanomedicine, whereas the use of the peripheral route has been unnoticed.…”

Section: Discussionmentioning

confidence: 99%

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Ion Permeability of the Nuclear Pore Complex and Ion-Induced Macromolecular Permeation as Studied by Scanning Electrochemical and Fluorescence Microscopy

et al. 2014

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Efficient delivery of therapeutic macromolecules and nanomaterials into the nucleus is imperative for gene therapy and nanomedicine. Nucleocytoplasmic molecular transport, however, is tightly regulated by the nuclear pore complex (NPC) with the hydrophobic transport barriers based on phenylalanine and glycine repeats. Herein, we apply scanning electrochemical microscopy (SECM) to quantitatively study the permeability of the NPCs to small probe ions with a wide range of hydrophobicity as a measure of their hydrophobic interactions with the transport barriers. Amperometric detection of the redox-inactive probe ions is enabled by using the ion-selective SECM tips based on the micropipet- or nanopipet-supported interfaces between two immiscible electrolyte solutions. The remarkably high ion permeability of the NPCs is successfully measured by SECM and theoretically analyzed. This analysis demonstrates that the ion permeability of the NPCs is determined by the dimensions and density of the nanopores without a significant effect of the transport barriers on the transported ions. Importantly, the weak ion–barrier interactions become significant at sufficiently high concentrations of extremely hydrophobic ions, i.e., tetraphenylarsonium and perfluorobutylsulfonate, to permeabilize the NPCs to naturally impermeable macromolecules. Dependence of ion-induced permeabilization of the NPC on the pathway and mode of macromolecular transport is studied by using fluorescence microscopy to obtain deeper insights into the gating mechanism of the NPC as the basis of a new transport model.

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Section: Results and Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ion Permeability of the Nuclear Pore Complex and Ion-Induced Macromolecular Permeation as Studied by Scanning Electrochemical and Fluorescence Microscopy

et al. 2014

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“…We designed alkyl (C2, C4, C6, and C8)-head PEG derivatives (alkyl-head PEG) as flexible molecules responsive to solvent change (Scheme ). The alkyl-head PEGs were synthesized according to our previous reports with some modifications (see details in Supporting Information). First, we examined the water contact angles of self-assembled monolayers (SAMs) of PEG derivatives on a gold substrate.…”

Section: Resultsmentioning

confidence: 99%

Hydrophilic Gold Nanoparticles Adaptable for Hydrophobic Solvents

et al. 2012

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Surface ligand molecules enabling gold nanoparticles to disperse in both polar and nonpolar solvents through changes in conformation are presented. Gold nanoparticles coated with alkyl-head-capped PEG derivatives were initially well dispersed in water through exposure of the PEG residue (bent form). When chloroform was added to the aqueous solution of gold nanoparticles, the gold nanoparticles were transferred from an aqueous to a chloroform phase through exposure of the alkyl-head residue (straight form). The conformational change (bent to straight form) of immobilized ligands in response to the polarity of the solvents was supported by NMR analyses and water contact angles.

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Bioinspired Cell Nuclear Nanotransporters Generated by Self‐Assembly of Amphiphilic Polysaccharide‐Amino Acid Derivatives Conjugates

et al. 2019

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Development of nanomaterials that surely transport functional biomacromolecules and bioactive synthetic compounds into the cell nucleus must be promising for the generation of nuclear‐targeting new technologies. However, the development of nuclear transporting nanomaterials thus still remains a significant challenge, because molecular transport between the cytoplasm and the nucleus of a eukaryotic cell is strictly regulated by the sole gateway through the nuclear envelope, the nuclear pore complexes (NPCs). Here, the rational design of novel artificial nuclear nanotransporters (NucPorters), inspired by importin, naturally occurring nuclear transporters is shown. The NucPorter is generated by simple molecular design: self‐assembly of amphiphilic polymers, where a few numbers of hydrophobic amino‐acid derivatives with phenyl groups are conjugated to negatively charged hydrophilic heparin. The NucPorter can mimic essential structural and chemical features of importin machinery to pass through the NPCs. Importantly, the NucPorter demonstrates remarkable rapid and high efficient nuclear transport in cultured cells, tissue/organ, and living mice. Moreover, the NucPorter successfully imports both enzymes and synthetic anticancer drugs into the nucleus while maintaining their bioactivity. Thus, the NucPorter provides a promising new route to generate innovative nuclear‐targeting medicines, diagnostics, cell imaging and engineering techniques, and drug delivery systems.

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Nuclear transport facilitated by the interaction between nuclear pores and carbohydrates

Cited by 4 publications

References 44 publications

Ion Permeability of the Nuclear Pore Complex and Ion-Induced Macromolecular Permeation as Studied by Scanning Electrochemical and Fluorescence Microscopy

Ion Permeability of the Nuclear Pore Complex and Ion-Induced Macromolecular Permeation as Studied by Scanning Electrochemical and Fluorescence Microscopy

Hydrophilic Gold Nanoparticles Adaptable for Hydrophobic Solvents

Bioinspired Cell Nuclear Nanotransporters Generated by Self‐Assembly of Amphiphilic Polysaccharide‐Amino Acid Derivatives Conjugates

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