Natively Unfolded Nucleoporins Gate Protein Diffusion across the Nuclear Pore Complex

Patel, Samir S.; Belmont, Brian J.; Sante, Joshua M.; Rexach, Michael

doi:10.1016/j.cell.2007.01.044

Cited by 537 publications

(708 citation statements)

References 28 publications

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“…We observed interactions between Arx1 and Nup100, Nup116¤ and Nup57 ( Figure 7A). As a control we recapitulated the previously reported homotypic interaction of Nup116 FG domains ( Figure 7A) as well as interactions of Nup116 with other Nup FG domains (data not shown; Patel et al, 2007). These results support the previous biochemical identification of Arx1 nucleoporin association.…”

Section: Arx1 Physically Interacts With Nucleoporinssupporting

confidence: 78%

“…Thus, the ribosomal subunits might also employ multiple receptors. In addition, the channel of the NPC is comprised of disordered FG repeat-containing nucleoporins that form a mesh through weak hydrophobic interactions (Ribbeck and Gorlich, 2001;Denning et al, 2003;Patel et al, 2007). The highly electronegative ribosomal subunits likely require additional proteins to present hydrophobic surfaces that can partition into this milieu.…”

Section: Introductionmentioning

confidence: 99%

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Arx1 Is a Nuclear Export Receptor for the 60S Ribosomal Subunit in Yeast

Hung

Patel

et al. 2008

MBoC

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We previously showed that nuclear export of the large (60S) ribosomal subunit relies on Nmd3 in a Crm1-dependent manner. Recently the general mRNA export factor, the Mtr2/Mex67 heterodimer, was shown to act as an export receptor in parallel with Crm1. These observations raise the possibility that nuclear export of the 60S subunit in Saccharomyces cerevisiae requires multiple export receptors. Here, we show that the previously characterized 60S subunit biogenesis factor, Arx1, also acts as an export receptor for the 60S subunit. We found that deletion of ARX1 was synthetic lethal with nmd3 and mtr2 mutants and was synthetic sick with several nucleoporin mutants. Deletion of ARX1 led to accumulation of pre-60S particles in the nucleus that were enriched for Nmd3, Crm1, Mex67, and Mtr2, suggesting that in the absence of Arx1, 60S export is impaired even though the subunit is loaded with export receptors. Finally, Arx1 interacted with several nucleoporins in yeast two-hybrid as well as in vitro assays. These results show that Arx1 can directly bridge the interaction between the pre-60S particle and the NPC and thus is a third export receptor for the 60S subunit in yeast.

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Section: Arx1 Physically Interacts With Nucleoporinssupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Arx1 Is a Nuclear Export Receptor for the 60S Ribosomal Subunit in Yeast

Hung

Patel

et al. 2008

MBoC

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“…It has been suggested that the two main FG repeat types (“FxFG/FG” and “GLFG”) are segregated in the NPC to define functionally distinct zones of the gating machinery 30 . In agreement, we find the FxFG/FG-type repeats to be enriched in the nuclear and cytoplasmic peripheries of the NPC, where the RNA-associating export platform and basket reside (Fig.…”

Section: Resultsmentioning

confidence: 99%

Integrative structure and functional anatomy of a nuclear pore complex

Kim

Fernández-Martı́nez

Nudelman

et al. 2018

Nature

490

894

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Summary Despite the central role of Nuclear Pore Complexes (NPCs) as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm, their large size and dynamic nature have impeded a full structural and functional elucidation. Here, we have determined a subnanometer precision structure for the entire 552-protein yeast NPC by satisfying diverse data including stoichiometry, a cryo-electron tomography map, and chemical cross-links. The structure reveals the NPC’s functional elements in unprecedented detail. The NPC is built of sturdy diagonal columns to which are attached connector cables, imbuing both strength and flexibility, while tying together all other elements of the NPC, including membrane-interacting regions and RNA processing platforms. Inwardly-directed anchors create a high density of transport factor-docking Phe-Gly repeats in the central channel, organized in distinct functional units. Taken together, this integrative structure allows us to rationalize the architecture, transport mechanism, and evolutionary origins of the NPC.

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“…In opisthokonts, there are also only a few major FG repeat flavors, the majority of which fall into the category of either "GLFG"-like or "FxFG"-like. 44,45 We also know that there are 2 major kinds of transport factor: karyopherin-like, and nonkaryopherin-like, with very different preferences for FG repeat flavors. 46,47 Certainly, trypanosomes show us that FG flavor may not necessarily be all about nucleocytoplasmic positioning or imparting a directionality to nuclear transport.…”

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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Natively Unfolded Nucleoporins Gate Protein Diffusion across the Nuclear Pore Complex

Cited by 537 publications

References 28 publications

Arx1 Is a Nuclear Export Receptor for the 60S Ribosomal Subunit in Yeast

Arx1 Is a Nuclear Export Receptor for the 60S Ribosomal Subunit in Yeast

Integrative structure and functional anatomy of a nuclear pore complex

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

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