The nuclear basket proteins Mlp1p and Mlp2p are part of a dynamic interactome including Esc1p and the proteasome

Niepel, Mario; Molloy, Kelly R.; Williams, Rosemary; Farr, Julia C.; Meinema, Anne C; Vecchietti, Nicholas; Cristea, Ileana M.; Chait, Brian T.; Rout, Michael P.; Strambio‐De‐Castillia, Caterina

doi:10.1091/mbc.e13-07-0412

Cited by 108 publications

(167 citation statements)

References 106 publications

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“…38,39 In the opisthokonts and plants, the nuclear basket is composed of large (»200-250 kDa) coiled coil proteins, that associate with and coordinate several nuclear peripheral processes, thereby extending NPC functionality. 36,62,[75][76][77][78] Although the 2 nuclear basket proteins are much smaller (»100kDa) in trypanosomes, our study showed by iEM, that they extend an average of 36nm into the nucleoplasm from the center of the TbNPC. 5 Additionally, they have retained similar functions to those in other eukarya, by creating heterochromatin free zones around nuclear pores that are evident by electron microscopy in all eukaryotic nuclei, as well as recapitulating interactions with the spindle organizer.…”

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

confidence: 47%

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

confidence: 47%

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

Obado

Field

Rout

2017

Nucleus

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“…Predictions of the transmembrane domains obtained from SGD 105 ( Saccharomyces Genome Database; http://yeastgenome.org) and predictions of membrane binding motifs by the HeliQuest webserver 90,106 informed about their proximity to the pore membrane. Previous immuno-EM measurements 107 informed the end-to-end distance for Mlp1 and Mlp2. Low-resolution EM images of the NPC 44 informed the diameter of the distal basket ring (formed by Mlp1 and Mlp2).…”

Section: Methodsmentioning

confidence: 99%

“…The conformations of Mlp1 and Mlp2 each were restrained by an upper harmonic bound at 350 Å and a lower harmonic bound at 230 Å on the distance between the N-terminal and C-terminal beads, based on immuno-EM measurements 107 . In addition, the radius of the distal basket ring was restrained by an upper harmonic bound at 170 Å and a lower harmonic bound at 130 Å on the radial coordinates of the C-terminal beads of Mlp1 and Mlp2, based on low-resolution EM images of the NPC 44 .…”

Section: Methodsmentioning

confidence: 99%

Integrative structure and functional anatomy of a nuclear pore complex

Kim

Fernández-Martı́nez

Nudelman

et al. 2018

Nature

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479

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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“…Esc1 is still somewhat obscure. Recent work has shown that the protein associates with the Mlp proteins that form the nuclear basket of nuclear pore complexes, as well as a protein network on the inner nuclear membrane (Niepel et al 2013, and references therein). A second anchor is created by interaction of Sir4 with a nucleoporin, Nup170 (Van de Vosse et al 2013).…”

Section: Sir4 and Heterochromatin Anchoring At The Nuclear Membranementioning

confidence: 99%

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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Transcriptional silencing in Saccharomyces cerevisiae occurs at several genomic sites including the silent mating-type loci, telomeres, and the ribosomal DNA (rDNA) tandem array. Epigenetic silencing at each of these domains is characterized by the absence of nearly all histone modifications, including most prominently the lack of histone H4 lysine 16 acetylation. In all cases, silencing requires Sir2, a highly-conserved NAD + -dependent histone deacetylase. At locations other than the rDNA, silencing also requires additional Sir proteins, Sir1, Sir3, and Sir4 that together form a repressive heterochromatin-like structure termed silent chromatin. The mechanisms of silent chromatin establishment, maintenance, and inheritance have been investigated extensively over the last 25 years, and these studies have revealed numerous paradigms for transcriptional repression, chromatin organization, and epigenetic gene regulation. Studies of Sir2-dependent silencing at the rDNA have also contributed to understanding the mechanisms for maintaining the stability of repetitive DNA and regulating replicative cell aging. The goal of this comprehensive review is to distill a wide array of biochemical, molecular genetic, cell biological, and genomics studies down to the "nuts and bolts" of silent chromatin and the processes that yield transcriptional silencing.

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The nuclear basket proteins Mlp1p and Mlp2p are part of a dynamic interactome including Esc1p and the proteasome

Cited by 108 publications

References 106 publications

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

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

Integrative structure and functional anatomy of a nuclear pore complex

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

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