The Nuclear Pore Complex and Nuclear Transport

Wente, Susan R.; Rout, Michael P.

doi:10.1101/cshperspect.a000562

Cited by 615 publications

(638 citation statements)

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“…Their principal function is to allow free diffusion of small molecules, such as water/ions/peptides, and to block non-specific translocation of macromolecules that exceed 40kDa or a diameter larger than 5nm ( Aitchison & Rout, 2012; Wente & Rout, 2010). Translocation of larger macromolecules requires specific interactions with the NPC.…”

Section: Discussion/analysis Of the Literaturementioning

confidence: 99%

Intracellular Dynamics of the Ubiquitin-Proteasome-System

Chowdhury

Enenkel

2015

F1000Res

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The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum (ER) membranes. In prolonged quiescence, proteasome granules drop off the NE / ER membranes and migrate as stable organelles throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus.Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm.Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body’s cells.

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Section: Discussion/analysis Of the Literaturementioning

confidence: 99%

Intracellular Dynamics of the Ubiquitin-Proteasome-System

Chowdhury

Enenkel

2015

F1000Res

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“…[3][4][5][6][7][8][9][10][11] Poms and the core scaffold form the major structural framework while FG-Nups establish the permeability barrier of the NPC and facilitate nucleocytoplasmic transport through interactions with soluble transport factors (karyopherins), with directionality dependent on a Ran GTP/GDP gradient. 12 There is extremely low sequence similarity between excavate and opisthokont Nups. 4 Despite this, trypanosome Nups share a remarkable architectural and domain organization with opisthokonts and plants, highlighting that structural considerations such as detailed fold arrangements are key to the function of these proteins (Table 1).…”

Section: Copy and Paste: The Npc's Scaffold Arose Through Ancient Dupmentioning

confidence: 99%

“…12 Approximately one third of FGNups in opisthokonts exhibit a biased localization within the NPC, being present either on the cytoplasmic side or the nucleoplasmic side of the pore. 9,36 This asymmetry is required for aspects of NPC function, especially mRNA export, which relies on the cytoplasmically biased Nup82 complex for messenger ribonucleoproteins (mRNPs) remodeling before release into the cytoplasm for translation by ribosomes.…”

Section: Tms and Alps: Multiple Ways To Tether A Leviathanmentioning

confidence: 99%

Comparative interactomics provides evidence for functional specialization of the nuclear pore complex

Obado

Field

Rout

2017

Nucleus

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The core architecture of the eukaryotic cell was established well over one billion years ago, and is largely retained in all extant lineages. However, eukaryotic cells also possess lineagespecific features, frequently keyed to specific functional requirements. One quintessential core eukaryotic structure is the nuclear pore complex (NPC), responsible for regulating exchange of macromolecules between the nucleus and cytoplasm as well as acting as a nuclear organizational hub. NPC architecture has been best documented in one eukaryotic supergroup, the Opisthokonts (e.g. Saccharomyces cerevisiae and Homo sapiens), which although compositionally similar, have significant variations in certain NPC subcomplex structures. The variation of NPC structure across other taxa in the eukaryotic kingdom however, remains poorly understood. We explored trypanosomes, highly divergent organisms, and mapped and assigned their NPC proteins to specific substructures to reveal their NPC architecture. We showed that the NPC central structural scaffold is conserved, likely across all eukaryotes, but more peripheral elements can exhibit very significant lineage-specific losses, duplications or other alterations in their components. Amazingly, trypanosomes lack the major components of the mRNA export platform that are asymmetrically localized within yeast and vertebrate NPCs. Concomitant with this, the trypanosome NPC is ALMOST completely symmetric with the nuclear basket being the only major source of asymmetry. We suggest these features point toward a stepwise evolution of the NPC in which a coating scaffold first stabilized the pore after which selective gating emerged and expanded, leading to the addition of peripheral remodeling machineries on the nucleoplasmic and cytoplasmic sides of the pore.

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“…Every second, mixed within a rich biological milieu, essential proteins, RNAs and metabolites impinge, crowd and translocate across the nuclear envelope. 1 This process is termed nucleocytoplasmic transport, which proceeds through aqueous channels known as nuclear pore complexes (NPCs). 2 The modus operandi that facilitates the selectivity and speed of signal-specific cargoes through NPCs is one that continues to fascinate and confound in equal measure.…”

Section: Introductionmentioning

confidence: 99%