Function of the Nuclear Transport Machinery in Maintaining the Distinctive Compositions of the Nucleus and Cytoplasm

Stewart, Murray

doi:10.3390/ijms23052578

Cited by 23 publications

(14 citation statements)

References 86 publications

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“…Nuclear pore complexes (NPCs) represent a major hub in the eukaryotic cell by forming a selective barrier for the import and export of RNAs and proteins between the cytosol and nucleus 1,2 . It is however not trivial to assemble and maintain this essential protein complex.…”

Section: Introductionmentioning

confidence: 99%

Nucleoporin Nsp1 surveils the phase state of FG-Nups

Otto

Bergsma

Dekker

et al. 2023

Preprint

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Transport through the NPC relies on intrinsically disordered FG-Nups forming a selective barrier. Away from the NPC, FG-Nups readily form condensates and aggregates, and we address how this behavior is surveilled in cells. FG-Nups, including Nsp1, together with nuclear transport receptor Kap95, form a native cytosolic condensate in yeast. In aged cells this condensate disappears as cytosolic Nsp1 levels decline. Biochemical assays and modeling show that Nsp1 is a modulator of FG-Nup liquid-liquid phase separation, promoting a liquid-like state. Nsp1s presence in the cytosol and condensates is critical, as a reduction of cytosolic levels in young cells induces NPC assembly and transport defects and a general decline in protein quality control, all quantitatively mimicking aging phenotypes. Excitingly, these phenotypes can be rescued by cytosolic Nsp1. We conclude that Nsp1 is a phase state regulator that surveils FG-Nups and impacts general protein homeostasis.

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Section: Introductionmentioning

confidence: 99%

Nucleoporin Nsp1 surveils the phase state of FG-Nups

Otto

Bergsma

Dekker

et al. 2023

Preprint

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“…The architecture incorporating both types of FG nups has long been suggested by observations [10, 13, 14, 39], and is likely to be evolutionarily conserved from yeast to mammalian cells [13,66]. It has been proposed that the low density/low cohesion “vestibules” at the pore periphery enhance the capture of NTRs while the central more cohesive FG nups serve as the “permeability barrier” [45, 67]. Our results suggest another potential functional purpose of this architecture as it allows the NPC to take advantage of crowding to achieve more efficient transport on the single-molecule level.…”

Section: Discussionmentioning

confidence: 99%

Self-regulation of the nuclear pore complex enables clogging-free crowded transport

Zheng

Zilman

2022

Preprint

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Nuclear pore complexes (NPCs) are the main conduits for macromolecular transport into and out of the nucleus of eukaryotic cells. The central component of the NPC transport mechanism is an assembly of intrinsically disordered proteins (IDPs) that fills the NPC channel. The channel interior is further crowded by large numbers of simultaneously translocating cargo-carrying and free transport proteins. How the NPC can efficiently, rapidly and selectively transport varied cargoes in such crowded conditions remains ill understood. Past experimental results suggest that the NPC is surprisingly resistant to clogging and that transport may even become faster and more efficient as the concentration of transport protein increases. To understand the mechanisms behind these puzzling observations, we construct a computational model of the NPC comprising only a minimal set of commonly-accepted consensus features. This model qualitatively reproduces the previous experimental results and identifies self-regulating mechanisms that relieve crowding. We show that some of the crowding-alleviating mechanisms -- such as preventing saturation of the bulk flux -- are "robust" and rely on very general properties of crowded dynamics in confined channels, pertaining to a broad class of selective transport nanopores. By contrast, the counter-intuitive ability of the NPC to leverage crowding to achieve more efficient single molecule translocation is "fine-tuned" and relies on the particular spatial architecture of the IDP assembly in the NPC channel.

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“…The central selective channel acts as gatekeeper to regulate the transport of macromolecules. At present, there are two main hypotheses regarding the selective barrier regulating the transport of macromolecules, namely “selective phase” model and “brush” model [ 47 ].…”

Section: Sketch Of Plant Npcmentioning

confidence: 99%

Function of Nuclear Pore Complexes in Regulation of Plant Defense Signaling

Wang

Han

Guo

2022

IJMS

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In eukaryotes, the nucleus is the regulatory center of cytogenetics and metabolism, and it is critical for fundamental biological processes, including DNA replication and transcription, protein synthesis, and biological macromolecule transportation. The eukaryotic nucleus is surrounded by a lipid bilayer called the nuclear envelope (NE), which creates a microenvironment for sophisticated cellular processes. The NE is perforated by the nuclear pore complex (NPC), which is the channel for biological macromolecule bi-directional transport between the nucleus and cytoplasm. It is well known that NPC is the spatial designer of the genome and the manager of genomic function. Moreover, the NPC is considered to be a platform for the continual adaptation and evolution of eukaryotes. So far, a number of nucleoporins required for plant-defense processes have been identified. Here, we first provide an overview of NPC organization in plants, and then discuss recent findings in the plant NPC to elaborate on and dissect the distinct defensive functions of different NPC subcomponents in plant immune defense, growth and development, hormone signaling, and temperature response. Nucleoporins located in different components of NPC have their unique functions, and the link between the NPC and nucleocytoplasmic trafficking promotes crosstalk of different defense signals in plants. It is necessary to explore appropriate components of the NPC as potential targets for the breeding of high-quality and broad spectrum resistance crop varieties.

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Function of the Nuclear Transport Machinery in Maintaining the Distinctive Compositions of the Nucleus and Cytoplasm

Cited by 23 publications

References 86 publications

Nucleoporin Nsp1 surveils the phase state of FG-Nups

Nucleoporin Nsp1 surveils the phase state of FG-Nups

Self-regulation of the nuclear pore complex enables clogging-free crowded transport

Function of Nuclear Pore Complexes in Regulation of Plant Defense Signaling

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