Nuclear Pore Complex in Nanomedicine 2.0

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Microenvironment".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 4379

Special Issue Editor


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Guest Editor
WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
Interests: nuclear pore complex; nano-medicine; cancer; cell cycle; AFM; SRM
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Special Issue Information

Dear Colleagues,

Nuclear pore complexes (NPCs) are at the heart of many supply chain stations inside our cells. NPCs are composed of approximately 30 different proteins (termed nucleoporins) which are inserted on the nuclear envelope utilizing liquid–liquid phase separation (LLPS) with their multilayered spiderweb-like central channels to control macromolecule trafficking. During mitosis, nuclear envelope breakdown leads to the rapid disintegration of NPCs, allowing some NPC proteins to play crucial roles in the kinetochore structure, spindle bipolarity, and centrosome homeostasis. The aberrant functioning of nucleoporins (Nups) and NPCs has been linked with autoimmune diseases, viral infections, neurological diseases, cardiomyopathies, and cancers, especially leukemia. Additionally, post-translational modifications of NPC proteins/nucleoporins include a series of enzymatically driven chemical modifications ranging from glycosylation to SUMOylation, phosphorylation, ubiquitination, acetylation, methylation, and lipidation, as well as their inverse reactions, regulating our cells’ bio-macromolecule supply chains. More recently, several NPC proteins involved in other processes (e.g., cellular autophagy and programmed necrosis) have been implicated in controlling both innate and adaptive immune functions. In short, modulation of the NPC barrier grants a potential strategy for refining drug delivery system (DDS) meticulousness or improving the effectiveness of current chemotherapeutics. This second release of the Special Issue continues to focus on the importance of NPC homeostasis to the development of nanomedicine.

Prof. Dr. Richard W. Wong
Guest Editor

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Keywords

  • nuclear pore complexes
  • spider cobweb
  • tumor marker
  • LLPS
  • supply chain
  • nano-pores

Published Papers (3 papers)

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Research

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16 pages, 6002 KiB  
Article
An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy
by Yujia Qiu, Elma Sakinatus Sajidah, Sota Kondo, Shinnosuke Narimatsu, Muhammad Isman Sandira, Yoshiki Higashiguchi, Goro Nishide, Azuma Taoka, Masaharu Hazawa, Yuka Inaba, Hiroshi Inoue, Ayami Matsushima, Yuki Okada, Mitsutoshi Nakada, Toshio Ando, Keesiang Lim and Richard W. Wong
Cells 2024, 13(3), 279; https://doi.org/10.3390/cells13030279 - 02 Feb 2024
Viewed by 1207
Abstract
Nuclear pore complexes (NPCs) on the nuclear membrane surface have a crucial function in controlling the movement of small molecules and macromolecules between the cell nucleus and cytoplasm through their intricate core channel resembling a spiderweb with several layers. Currently, there are few [...] Read more.
Nuclear pore complexes (NPCs) on the nuclear membrane surface have a crucial function in controlling the movement of small molecules and macromolecules between the cell nucleus and cytoplasm through their intricate core channel resembling a spiderweb with several layers. Currently, there are few methods available to accurately measure the dynamics of nuclear pores on the nuclear membranes at the nanoscale. The limitation of traditional optical imaging is due to diffraction, which prevents achieving the required resolution for observing a diverse array of organelles and proteins within cells. Super-resolution techniques have effectively addressed this constraint by enabling the observation of subcellular components on the nanoscale. Nevertheless, it is crucial to acknowledge that these methods often need the use of fixed samples. This also raises the question of how closely a static image represents the real intracellular dynamic system. High-speed atomic force microscopy (HS-AFM) is a unique technique used in the field of dynamic structural biology, enabling the study of individual molecules in motion close to their native states. Establishing a reliable and repeatable technique for imaging mammalian tissue at the nanoscale using HS-AFM remains challenging due to inadequate sample preparation. This study presents the rapid strainer microfiltration (RSM) protocol for directly preparing high-quality nuclei from the mouse brain. Subsequently, we promptly utilize HS-AFM real-time imaging and cinematography approaches to record the spatiotemporal of nuclear pore nano-dynamics from the mouse brain. Full article
(This article belongs to the Special Issue Nuclear Pore Complex in Nanomedicine 2.0)
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23 pages, 6746 KiB  
Article
Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of Drosophila Male Meiosis
by Kanta Yamazoe and Yoshihiro H. Inoue
Cells 2023, 12(22), 2611; https://doi.org/10.3390/cells12222611 - 11 Nov 2023
Cited by 1 | Viewed by 909
Abstract
The cyclin-dependent kinase 1 (Cdk1)–cyclin B (CycB) complex plays critical roles in cell-cycle regulation. Before Drosophila male meiosis, CycB is exported from the nucleus to the cytoplasm via the nuclear porin 62kD (Nup62) subcomplex of the nuclear pore complex. When this export is [...] Read more.
The cyclin-dependent kinase 1 (Cdk1)–cyclin B (CycB) complex plays critical roles in cell-cycle regulation. Before Drosophila male meiosis, CycB is exported from the nucleus to the cytoplasm via the nuclear porin 62kD (Nup62) subcomplex of the nuclear pore complex. When this export is inhibited, Cdk1 is not activated, and meiosis does not initiate. We investigated the mechanism that controls the cellular localization and activation of Cdk1. Cdk1–CycB continuously shuttled into and out of the nucleus before meiosis. Overexpression of CycB, but not that of CycB with nuclear localization signal sequences, rescued reduced cytoplasmic CycB and inhibition of meiosis in Nup62-silenced cells. Full-scale Cdk1 activation occurred in the nucleus shortly after its rapid nuclear entry. Cdk1-dependent centrosome separation did not occur in Nup62-silenced cells, whereas Cdk1 interacted with Cdk-activating kinase and Twine/Cdc25C in the nuclei of Nup62-silenced cells, suggesting the involvement of another suppression mechanism. Silencing of roughex rescued Cdk1 inhibition and initiated meiosis. Nuclear export of Cdk1 ensured its escape from inhibition by a cyclin-dependent kinase inhibitor. The complex re-entered the nucleus via importin β at the onset of meiosis. We propose a model regarding the dynamics and activation mechanism of Cdk1–CycB to initiate male meiosis. Full article
(This article belongs to the Special Issue Nuclear Pore Complex in Nanomedicine 2.0)
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Review

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21 pages, 6619 KiB  
Review
Nuclear Delivery of Nanoparticle-Based Drug Delivery Systems by Nuclear Localization Signals
by Yuhan Nie, Guo Fu and Yuxin Leng
Cells 2023, 12(12), 1637; https://doi.org/10.3390/cells12121637 - 15 Jun 2023
Cited by 5 | Viewed by 1915
Abstract
Nanomedicine 2.0 refers to the next generation of nanotechnology-based medical therapies and diagnostic tools. This field focuses on the development of more sophisticated and precise nanoparticles (NPs) for targeted drug delivery, imaging, and sensing. It has been established that the nuclear delivery of [...] Read more.
Nanomedicine 2.0 refers to the next generation of nanotechnology-based medical therapies and diagnostic tools. This field focuses on the development of more sophisticated and precise nanoparticles (NPs) for targeted drug delivery, imaging, and sensing. It has been established that the nuclear delivery of NP-loaded drugs can increase their therapeutic efficacy. To effectively direct the NPs to the nucleus, the attachment of nuclear localization signals (NLSs) to NPs has been employed in many applications. In this review, we will provide an overview of the structure of nuclear pore complexes (NPCs) and the classic nuclear import mechanism. Additionally, we will explore various nanoparticles, including their synthesis, functionalization, drug loading and release mechanisms, nuclear targeting strategies, and potential applications. Finally, we will highlight the challenges associated with developing nucleus-targeted nanoparticle-based drug delivery systems (NDDSs) and provide insights into the future of NDDSs. Full article
(This article belongs to the Special Issue Nuclear Pore Complex in Nanomedicine 2.0)
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