scholarly journals Cargo transport through the nuclear pore complex at a glance

2021 ◽  
Vol 134 (2) ◽  
pp. jcs247874
Author(s):  
Giulia Paci ◽  
Joana Caria ◽  
Edward A. Lemke
Keyword(s):  
Nuclear Pore Complex ◽  
Nuclear Transport ◽  
Cell Cycle Control ◽  
Genetic Material ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Cargo Transport ◽  
Transport Receptors ◽  
Bidirectional Transport ◽  
Transport Of Macromolecules

ABSTRACTBidirectional transport of macromolecules across the nuclear envelope is a hallmark of eukaryotic cells, in which the genetic material is compartmentalized inside the nucleus. The nuclear pore complex (NPC) is the major gateway to the nucleus and it regulates nucleocytoplasmic transport, which is key to processes including transcriptional regulation and cell cycle control. Accordingly, components of the nuclear transport machinery are often found to be dysregulated or hijacked in diseases. In this Cell Science at a Glance article and accompanying poster, we provide an overview of our current understanding of cargo transport through the NPC, from the basic transport signals and machinery to more emerging aspects, all from a ‘cargo perspective’. Among these, we discuss the transport of large cargoes (>15 nm), as well as the roles of different cargo properties to nuclear transport, from size and number of bound nuclear transport receptors (NTRs), to surface and mechanical properties.

scholarly journals Model Inspired by Nuclear Pore Complex Suggests Possible Roles for Nuclear Transport Receptors in Determining Its Structure

2013 ◽  
Vol 105 (12) ◽  
pp. 2781-2789 ◽  
Author(s):  
Dino Osmanović ◽  
Ian J. Ford ◽  
Bart W. Hoogenboom
Keyword(s):  
Nuclear Pore Complex ◽  
Nuclear Transport ◽  
Nuclear Pore ◽  
Transport Receptors

Nucleocytoplasmic transport in yeast: a few roles for many actors

2010 ◽  
Vol 38 (1) ◽  
pp. 273-277 ◽  
Author(s):  
Jindriska Fiserova ◽  
Martin W. Goldberg
Keyword(s):  
Nuclear Pore Complex ◽  
Model Organism ◽  
Nucleocytoplasmic Transport ◽  
Present Review ◽  
Eukaryotic Cells ◽  
Nuclear Pore ◽  
Controlled Processes ◽  
Bidirectional Transport

Eukaryotic cells have developed a series of highly controlled processes of transport between the nucleus and cytoplasm. The present review focuses on the latest advances in our understanding of nucleocytoplasmic exchange of molecules in yeast, a widely studied model organism in the field. It concentrates on the role of individual proteins such as nucleoporins and karyopherins in the translocation process and relates this to how the organization of the nuclear pore complex effectively facilitates the bidirectional transport between the two compartments.

Getting across the nuclear pore complex: new insights into nucleocytoplasmic transportThis paper is one of a selection of papers published in this Special Issue, entitled The Nucleus: A Cell Within A Cell.

2006 ◽  
Vol 84 (3-4) ◽  
pp. 499-507 ◽  
Author(s):  
Daniel Stoffler ◽  
Kyrill Schwarz-Herion ◽  
Ueli Aebi ◽  
Birthe Fahrenkrog
Keyword(s):  
Nuclear Pore Complex ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Special Issue ◽  
The Past ◽  
Transport Receptors ◽  
A Cell ◽  
New Evidence ◽  
Retention Signal ◽  
Selection Of

Small ions and molecules can traverse the nuclear pore complex (NPC) simply by diffusion, whereas larger proteins and RNAs require specific signals and factors that facilitate their passage through the NPC. Our understanding of the factors that participate and regulate nucleocytoplasmic transport has increased tremendously over the past years, whereas the actual translocation step through the NPC has remained largely unclear. Here, we present and discuss recent findings on the interaction between the NPC and transport receptors and provide new evidence that the NPC acts as a constrained diffusion pore for molecules and particles without retention signal and as an affinity gate for signal-bearing cargos.

scholarly journals Measuring and Interpreting Nuclear Transport in Neurodegenerative Disease—The Example of C9orf72 ALS

2021 ◽  
Vol 22 (17) ◽  
pp. 9217
Author(s):  
Marije F. W. Semmelink ◽  
Anton Steen ◽  
Liesbeth M. Veenhoff
Keyword(s):  
Nuclear Pore Complex ◽  
Nuclear Transport ◽  
Nucleocytoplasmic Transport ◽  
Current Data ◽  
Positive Answer ◽  
Future Research ◽  
Nuclear Pore ◽  
Specific Proteins ◽  
Open Question ◽  
Kinetics Of

Transport from and into the nucleus is essential to all eukaryotic life and occurs through the nuclear pore complex (NPC). There are a multitude of data supporting a role for nuclear transport in neurodegenerative diseases, but actual transport assays in disease models have provided diverse outcomes. In this review, we summarize how nuclear transport works, which transport assays are available, and what matters complicate the interpretation of their results. Taking a specific type of ALS caused by mutations in C9orf72 as an example, we illustrate these complications, and discuss how the current data do not firmly answer whether the kinetics of nucleocytoplasmic transport are altered. Answering this open question has far-reaching implications, because a positive answer would imply that widespread mislocalization of proteins occurs, far beyond the reported mislocalization of transport reporters, and specific proteins such as FUS, or TDP43, and thus presents a challenge for future research.

scholarly journals Molecular determinants of large cargo transport into the nucleus

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Giulia Paci ◽  
Tiantian Zheng ◽  
Joana Caria ◽  
Anton Zilman ◽  
Edward A Lemke
Keyword(s):  
Nuclear Import ◽  
Nucleocytoplasmic Transport ◽  
Biophysical Model ◽  
Nuclear Pore ◽  
Cargo Transport ◽  
Transport Receptors ◽  
Molecular Determinants ◽  
Quantitative Understanding ◽  
Kinetics Of

Nucleocytoplasmic transport is tightly regulated by the nuclear pore complex (NPC). Among the thousands of molecules that cross the NPC, even very large (>15 nm) cargoes such as pathogens, mRNAs and pre-ribosomes can pass the NPC intact. For these cargoes, there is little quantitative understanding of the requirements for their nuclear import, especially the role of multivalent binding to transport receptors via nuclear localisation sequences (NLSs) and the effect of size on import efficiency. Here, we assayed nuclear import kinetics of 30 large cargo models based on four capsid-like particles in the size range of 17–36 nm, with tuneable numbers of up to 240 NLSs. We show that the requirements for nuclear transport can be recapitulated by a simple two-parameter biophysical model that correlates the import flux with the energetics of large cargo transport through the NPC. Together, our results reveal key molecular determinants of large cargo import in cells.

scholarly journals Scaffold nucleoporins Nup188 and Nup192 share structural and functional properties with nuclear transport receptors

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Kasper R Andersen ◽  
Evgeny Onischenko ◽  
Jeffrey H Tang ◽  
Pravin Kumar ◽  
James Z Chen ◽  
...  
Keyword(s):  
Nuclear Transport ◽  
Evolutionary Relationship ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Rotational Axis ◽  
Nuclear Pore Complexes ◽  
Facilitated Diffusion ◽  
Structural And Functional Properties ◽  
Transport Receptors ◽  
Pore Complexes

Nucleocytoplasmic transport is mediated by nuclear pore complexes (NPCs) embedded in the nuclear envelope. About 30 different proteins (nucleoporins, nups) arrange around a central eightfold rotational axis to build the modular NPC. Nup188 and Nup192 are related and evolutionary conserved, large nucleoporins that are part of the NPC scaffold. Here we determine the structure of Nup188. The protein folds into an extended stack of helices where an N-terminal 130 kDa segment forms an intricate closed ring, while the C-terminal region is a more regular, superhelical structure. Overall, the structure has distant similarity with flexible S-shaped nuclear transport receptors (NTRs). Intriguingly, like NTRs, both Nup188 and Nup192 specifically bind FG-repeats and are able to translocate through NPCs by facilitated diffusion. This blurs the existing dogma of a clear distinction between stationary nups and soluble NTRs and suggests an evolutionary relationship between the NPC and the soluble nuclear transport machinery.

Nucleocytoplasmic transport of macromolecules

1997 ◽  
Vol 61 (2) ◽  
pp. 193-211
Author(s):  
A H Corbett ◽  
P A Silver
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Transport ◽  
Bound State ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Yeast Saccharomyces Cerevisiae ◽  
Soluble Factors ◽  
Pore Complexes ◽  
Transport Of Macromolecules

Nucleocytoplasmic transport is a complex process that consists of the movement of numerous macromolecules back and forth across the nuclear envelope. All macromolecules that move in and out of the nucleus do so via nuclear pore complexes that form large proteinaceous channels in the nuclear envelope. In addition to nuclear pores, nuclear transport of macromolecules requires a number of soluble factors that are found both in the cytoplasm and in the nucleus. A combination of biochemical, genetic, and cell biological approaches have been used to identify and characterize the various components of the nuclear transport machinery. Recent studies have shown that both import to and export from the nucleus are mediated by signals found within the transport substrates. Several studies have demonstrated that these signals are recognized by soluble factors that target these substrates to the nuclear pore. Once substrates have been directed to the pore, most transport events depend on a cycle of GTP hydrolysis mediated by the small Ras-like GTPase, Ran, as well as other proteins that regulate the guanine nucleotide-bound state of Ran. Many of the essential factors have been identified, and the challenge that remains is to determine the exact mechanism by which transport occurs. This review attempts to present an integrated view of our current understanding of nuclear transport while highlighting the contributions that have been made through studies with genetic organisms such as the budding yeast, Saccharomyces cerevisiae.

Nanomechanical Basis of Selective Gating by the Nuclear Pore Complex

Science ◽  
2007 ◽  
Vol 318 (5850) ◽  
pp. 640-643 ◽  
Author(s):  
Roderick Y. H. Lim ◽  
Birthe Fahrenkrog ◽  
Joachim Köser ◽  
Kyrill Schwarz-Herion ◽  
Jie Deng ◽  
...  
Keyword(s):  
Nuclear Pore Complex ◽  
Polymer Brush ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Guanosine Triphosphate ◽  
Binding Interactions ◽  
Molecular Conformations ◽  
Cargo Transport ◽  
Transport Receptor

The nuclear pore complex regulates cargo transport between the cytoplasm and the nucleus. We set out to correlate the governing biochemical interactions to the nanoscopic responses of the phenylalanineglycine (FG)–rich nucleoporin domains, which are involved in attenuating or promoting cargo translocation. We found that binding interactions with the transport receptor karyopherin-β1 caused the FG domains of the human nucleoporin Nup153 to collapse into compact molecular conformations. This effect was reversed by the action of Ran guanosine triphosphate, which returned the FG domains into a polymer brush-like, entropic barrier conformation. Similar effects were observed in Xenopus oocyte nuclei in situ. Thus, the reversible collapse of the FG domains may play an important role in regulating nucleocytoplasmic transport.

Structure, assembly and interactions of the nuclear lamina and the nuclear pore complex

1992 ◽  
Vol 50 (1) ◽  
pp. 490-491
Author(s):  
N. Panté ◽  
M. Jarnik ◽  
E. Heitlinger ◽  
U. Aebi
Keyword(s):  
Nuclear Pore Complex ◽  
Divalent Cations ◽  
Nuclear Lamina ◽  
Dynamic Structure ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Cytoplasmic Filaments ◽  
Radial Spokes ◽  
Nuclear Ring ◽  
Central Plug

The nuclear pore complex (NPC) is a ∼120 MD supramolecular machine implicated in nucleocytoplasmic transport, that is embedded in the double-membraned nuclear envelope (NE). The basic framework of the ∼120 nm diameter NPC consists of a 32 MD cytoplasmic ring, a 66 MD ‘plug-spoke’ assembly, and a 21 MD nuclear ring. The ‘central plug’ seen in en face views of the NPC reveals a rather variable appearance indicating that it is a dynamic structure. Projecting from the cytoplasmic ring are 8 short, twisted filaments (Fig. 1a), whereas the nuclear ring is topped with a ‘fishtrap’ made of 8 thin filaments that join distally to form a fragile, 30-50 nm distal diameter ring centered above the NPC proper (Fig. 1b). While the cytoplasmic filaments are sensitive to proteases, they as well as the nuclear fishtraps are resistant to RNase treatment. Removal of divalent cations destabilizes the distal rings and thereby opens the fishtraps, addition causes them to reform. Protruding from the tips of the radial spokes into perinuclear space are ‘knobs’ that might represent the large lumenal domain of gp210, a membrane-spanning glycoprotein (Fig. 1c) which, in turn, may play a topogenic role in membrane folding and/or act as a membrane-anchoring site for the NPC. The lectin wheat germ agglutinin (WGA) which is known to recognize the ‘nucleoporins’, a family of glycoproteins having O-linked N-acetyl-glucosamine, is found in two locations on the NPC (Fig. 1. d-f): (i) whereas the cytoplasmic filaments appear unlabelled (Fig. 1d&e), WGA-gold labels sites between the central plug and the cytoplasmic ring (Fig. le; i.e., at a radius of 25-35 nm), and (ii) it decorates the distal ring of the nuclear fishtraps (Fig. 1, d&f; arrowheads).

Sign in / Sign up

Export Citation Format

Share Document