Metazoan nuclear pore complexes in gene regulation and genome stability DOI Creative Commons
Parisa Nobari, Valérie Doye, Charlène Boumendil

et al.

DNA repair, Journal Year: 2023, Volume and Issue: 130, P. 103565 - 103565

Published: Sept. 4, 2023

The nuclear pore complexes (NPCs), one of the hallmarks eukaryotic nuclei, allow selective transport macromolecules between cytoplasm and nucleus. Besides this canonical function, an increasing number additional roles have been attributed to NPCs their constituents, nucleoporins. Here we review recent insights into mechanisms by which nucleoporins affect transcription DNA repair in metazoans. In first part, discuss how gene expression can be affected localization genome-nucleoporin interactions at pores or "off-pores", role chromatin organization different scales, physical properties second contribution genome stability, including transport-dependent -independent functions positioning heterochromatic breaks regulation replication stress.

Language: Английский

Nuclear pore dysfunction and disease: a complex opportunity DOI Creative Commons
Charlotte M. Fare, Jeffrey D. Rothstein

Nucleus, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 21, 2024

The separation of genetic material from bulk cytoplasm has enabled the evolution increasingly complex organisms, allowing for development sophisticated forms life. However, this complexity created new categories dysfunction, including those related to movement between cellular compartments. In eukaryotic cells, nucleocytoplasmic trafficking is a fundamental biological process, and cumulative disruptions nuclear integrity transport are detrimental cell survival. This particularly true in post-mitotic neurons, where pore injury errors strongly associated with neurodegenerative disease. review, we summarize current understanding biology physiological pathological contexts discuss potential therapeutic approaches addressing dysfunctional transport.

Language: Английский

Citations

11
Nanoassemblies designed for efficient nuclear targeting DOI Creative Commons
Michal Skowicki, Shabnam Tarvirdipour, Manuel Kraus

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 211, P. 115354 - 115354

Published: June 12, 2024

One of the key aspects coping efficiently with complex pathological conditions is delivering desired therapeutic compounds precision in both space and time. Therefore, focus on nuclear-targeted delivery systems has emerged as a promising strategy high potential, particularly gene therapy cancer treatment. Here, we explore design supramolecular nanoassemblies vehicles to deliver specific nucleus, special polymer peptide-based carriers that expose nuclear localization signals. Such aim at maximizing concentration genetic agents within thereby optimizing treatment outcomes while minimizing off-target effects. A scenario conditions, including cellular uptake, endosomal escape, translocation, requires fine tuning nanocarriers' properties. First, introduce principles import role pore complexes reveal strategies for targeting nanosystems nucleus. Then, provide an overview cargoes rely optimal activity their integrity accumulation are crucial parameters consider when designing suitable system. Considering they early stages research, present various cargo-loaded peptide- promote targeting, emphasizing potential enhance response. Finally, briefly discuss further advancements more precise effective delivery.

Language: Английский

Citations

10
The chaperone DNAJB6 surveils FG-nucleoporins and is required for interphase nuclear pore complex biogenesis DOI
E. F. Elsiena Kuiper, Paola Gallardo, Tessa Bergsma

et al.

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(11), P. 1584 - 1594

Published: Oct. 27, 2022

Language: Английский

Citations

39
An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy DOI Creative Commons

Yujia Qiu,

Elma Sakinatus Sajidah, Sota Kondo

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 279 - 279

Published: Feb. 2, 2024

Nuclear pore complexes (NPCs) on the nuclear membrane surface have a crucial function in controlling movement of small molecules and macromolecules between cell nucleus cytoplasm through their intricate core channel resembling spiderweb with several layers. Currently, there are few methods available to accurately measure dynamics pores membranes at nanoscale. The limitation traditional optical imaging is due diffraction, which prevents achieving required resolution for observing diverse array organelles proteins within cells. Super-resolution techniques effectively addressed this constraint by enabling observation subcellular components Nevertheless, it acknowledge that these often need use fixed samples. This also raises question how closely static image represents real intracellular dynamic system. High-speed atomic force microscopy (HS-AFM) unique technique used field structural biology, study individual motion close native states. Establishing reliable repeatable mammalian tissue nanoscale using HS-AFM remains challenging inadequate sample preparation. presents rapid strainer microfiltration (RSM) protocol directly preparing high-quality nuclei from mouse brain. Subsequently, we promptly utilize real-time cinematography approaches record spatiotemporal nano-dynamics

Language: Английский

Citations

7
Exportin-1 functions as an adaptor for transcription factor-mediated docking of chromatin at the nuclear pore complex. DOI Creative Commons
Tiffany Ge,

Donna Garvey Brickner,

Kara Zehr

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 13, 2024

Nuclear pore proteins (Nups) in yeast, flies and mammals physically interact with hundreds or thousands of chromosomal sites, which impacts transcriptional regulation. In budding transcription factors mediate interaction Nups enhancers highly active genes. To define the molecular basis this mechanism, we exploited a separation-of-function mutation Gcn4 factor that blocks its nuclear complex (NPC) without altering DNA binding activation domains. SILAC mass spectrometry revealed reduces conserved export Crm1/Xpo1. Crm1 both interacts same sites as genome-wide is required for Nup2 to yeast genome.

Language: Английский

Citations

7
Strategies for the Viral Exploitation of Nuclear Pore Transport Pathways DOI Creative Commons
Xin Zhang, Keesiang Lim,

Yujia Qiu

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(2), P. 151 - 151

Published: Jan. 23, 2025

Viruses frequently exploit the host’s nucleocytoplasmic trafficking machinery to facilitate their replication and evade immune defenses. By encoding specialized proteins other components, they strategically target host nuclear transport receptors (NTRs) nucleoporins within spiderweb-like inner channel of pore complex (NPC), enabling efficient access nucleus. This review explores intricate mechanisms governing import export viral with a focus on interplay between factors determinants that are essential for these processes. Given pivotal role shuttling in life cycle, we also examine therapeutic strategies aimed at disrupting pathways. includes evaluating efficacy pharmacological inhibitors impairing assessing potential as antiviral treatments. Furthermore, emphasize need continued research develop targeted therapies leverage vulnerabilities trafficking. Emerging high-resolution techniques, such advanced imaging computational modeling, transforming our understanding dynamic interactions viruses NPC. These cutting-edge tools driving progress identifying novel opportunities uncovering deeper insights into pathogenesis. highlights importance advancements paving way innovative strategies.

Language: Английский

Citations

1
Volumetric Reconstruction of a Human Retinal Pigment Epithelial Cell Reveals Specialized Membranes and Polarized Distribution of Organelles DOI Creative Commons

Maximilian Lindell,

Deepayan Kar,

Aleksandra Sedova

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2023, Volume and Issue: 64(15), P. 35 - 35

Published: Dec. 22, 2023

Purpose: Despite the centrality of retinal pigment epithelium (RPE) in vision and retinopathy our picture RPE morphology is incomplete. With a volumetric reconstruction human ultrastructure, we aim to characterize major membranous features including apical processes their interactions with photoreceptor outer segments, basolateral infoldings, distribution intracellular organelles. Methods: A parafoveal sample was acquired from 21-year-old male organ donor. serial block-face scanning electron microscopy, tissue volume inner-outer segment junction basal captured. Surface membranes complete internal ultrastructure an individual cell were achieved combination manual automated segmentation methods. Results: In one cell, constitute 69% total surface area, through dense network over 3000 terminal branches. Single contact several photoreceptors. Basolateral infoldings facing choriocapillaris resemble elongated filopodia comprise 22% area. Membranous tubules sacs endoplasmic reticulum represent 20% body volume. layer mitochondria extends apically partly overlap electron-dense granules. Pores nuclear envelope form distinct pattern rows aligned chromatin. Conclusions: Specialized at side involved intercellular uptake transport 90% Together polarized organelles within body, these findings are relevant for clinical imaging, therapeutic approaches, disease pathomechanisms.

Language: Английский

Citations

17
Nuclear Import and Export of YAP and TAZ DOI Open Access

Michael Kofler,

András Kapùs

Cancers, Journal Year: 2023, Volume and Issue: 15(20), P. 4956 - 4956

Published: Oct. 12, 2023

Yes-associated Protein (YAP) and its paralog Transcriptional Coactivator with PDZ-binding Motif (TAZ) are major regulators of gene transcription/expression, primarily controlled by the Hippo pathway cytoskeleton. Integrating an array chemical mechanical signals, they impact growth, differentiation, regeneration. Accordingly, also play key roles in tumorigenesis metastasis formation. Their activity is regulated their localization, that is, pathway- and/or cytoskeleton-controlled cytosolic or nuclear sequestration. While many details such prevailing retention models have been elucidated, much less known about actual traffic: import export. Although size not far from cutoff for passive diffusion through pore complex (NPC), do contain any classic localization (NLS) export signal (NES), evidence has accumulating shuttling involves mediated thus regulatable/targetable processes. The aim this review to summarize emerging information/concepts nucleocytoplasmic shuttling, encompassing relevant structural requirements (NLS, NES), transport receptors (NTRs, karyophererins), NPC components, along potential mechanisms regulation. dissecting vs. often challenging, picture suggests YAP/TAZ shuttles across via multiple, non-exclusive, mechanisms, constituting a novel intriguing facet biology.

Language: Английский

Citations

15
An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity DOI
Nicholas R. Ader, Linda Chen, Ivan V. Surovtsev

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(10), P. 1465 - 1477

Published: Oct. 1, 2023

Language: Английский

Citations

14
Nuclear and degradative functions of the ESCRT-III pathway: implications for neurodegenerative disease DOI Creative Commons

Olivia Keeley,

Alyssa N. Coyne

Nucleus, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 3, 2024

The ESCRT machinery plays a pivotal role in membrane-remodeling events across multiple cellular processes including nuclear envelope repair and reformation, pore complex surveillance, endolysosomal trafficking, neuronal pruning. Alterations ESCRT-III functionality have been associated with neurodegenerative diseases Frontotemporal Dementia (FTD), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's Disease (AD). In addition, mutations specific proteins identified FTD/ALS. Thus, understanding how disruptions the fundamental functions of this pathway its individual protein components human central nervous system (CNS) may offer valuable insights into mechanisms underlying disease pathogenesis identification potential therapeutic targets. review, we discuss components, dynamics, functions, focus on pathway. explore implications altered function for neurodegeneration primary emphasis surveillance trafficking within CNS.

Language: Английский

Citations

6