scholarly journals Nucleophagy—Implications for Microautophagy and Health

2020 ◽  
Vol 21 (12) ◽  
pp. 4506 ◽  
Author(s):  
Florian Bo Otto ◽  
Michael Thumm
Keyword(s):  
Nuclear Material ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Unique Role ◽  
The Core ◽  
Subsequent Degradation ◽  
Autophagic Degradation ◽  
Membrane Contact ◽  
Pore Complexes

Nucleophagy, the selective subtype of autophagy that targets nuclear material for autophagic degradation, was not only shown to be a model system for the study of selective macroautophagy, but also for elucidating the role of the core autophagic machinery within microautophagy. Nucleophagy also emerged as a system associated with a variety of disease conditions including cancer, neurodegeneration and ageing. Nucleophagic processes are part of natural cell development, but also act as a response to various stress conditions. Upon releasing small portions of nuclear material, micronuclei, the autophagic machinery transfers these micronuclei to the vacuole for subsequent degradation. Despite sharing many cargos and requiring the core autophagic machinery, recent investigations revealed the aspects that set macro- and micronucleophagy apart. Central to the discrepancies found between macro- and micronucleophagy is the nucleus vacuole junction, a large membrane contact site formed between nucleus and vacuole. Exclusion of nuclear pore complexes from the junction and its exclusive degradation by micronucleophagy reveal compositional differences in cargo. Regarding their shared reliance on the core autophagic machinery, micronucleophagy does not involve normal autophagosome biogenesis observed for macronucleophagy, but instead maintains a unique role in overall microautophagy, with the autophagic machinery accumulating at the neck of budding vesicles.

scholarly journals Autophagy of the Nucleus in Health and Disease

2022 ◽  
Vol 9 ◽  
Author(s):  
Georgios Konstantinidis ◽  
Nektarios Tavernarakis
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cellular Differentiation ◽  
Nuclear Material ◽  
Nuclear Pore ◽  
Common Denominator ◽  
Nuclear Pore Complexes ◽  
The Core ◽  
Health And Disease ◽  
Pore Complexes

Nucleophagy is an organelle-selective subtype of autophagy that targets nuclear material for degradation. The macroautophagic delivery of micronuclei to the vacuole, together with the nucleus-vacuole junction-dependent microautophagic degradation of nuclear material, were first observed in yeast. Nuclear pore complexes and ribosomal DNA are typically excluded during conventional macronucleophagy and micronucleophagy, indicating that degradation of nuclear cargo is tightly regulated. In mammals, similarly to other autophagy subtypes, nucleophagy is crucial for cellular differentiation and development, in addition to enabling cells to respond to various nuclear insults and cell cycle perturbations. A common denominator of all nucleophagic processes characterized in diverse organisms is the dependence on the core autophagic machinery. Here, we survey recent studies investigating the autophagic processing of nuclear components. We discuss nucleophagic events in the context of pathology, such as neurodegeneration, cancer, DNA damage, and ageing.

scholarly journals Distinct Basket Nucleoporins roles in Nuclear Pore Function and Gene Expression: Tpr is an integral component of the TREX-2 mRNA export pathway

2019 ◽  
Author(s):  
Vasilisa Aksenova ◽  
Hang Noh Lee ◽  
Alexandra Smith ◽  
Shane Chen ◽  
Prasanna Bhat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Export ◽  
Protein Modification ◽  
Mrna Export ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nucleocytoplasmic Trafficking ◽  
Pore Complexes ◽  
Slow Turnover

AbstractNuclear pore complexes (NPCs) are important for many processes beyond nucleocytoplasmic trafficking, including protein modification, chromatin remodeling, transcription, mRNA processing and mRNA export. The multi-faceted nature of NPCs and the slow turnover of their components has made it difficult to understand the role of basket nucleoporins (Nup153, Nup50 and Tpr) in these diverse processes. To address this question, we used anAuxin-InducedDegron (AID) system to distinguish roles of basket nucleoporins: Loss of individual nucleoporins caused distinct alteration in patterns of nucleocytoplasmic trafficking and gene expression. Importantly, Tpr elimination caused rapid and pronounced changes in transcriptomic profiles within two hours of auxin addition. These changes were dissimilar to shifts observed after loss of Nup153 or Nup50, but closely related to changes after depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, GANP association to NPCs was specifically disrupted upon TPR depletion. Together, our findings demonstrate a unique and pivotal role of Tpr in regulating gene expression through GANP- and/or NXF1-dependent mRNA nuclear export.

scholarly journals Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Vasilisa Aksenova ◽  
Alexandra Smith ◽  
Hangnoh Lee ◽  
Prasanna Bhat ◽  
Caroline Esnault ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Export ◽  
Mrna Turnover ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nucleocytoplasmic Trafficking ◽  
Cellular Functions ◽  
Pore Complexes ◽  
Slow Turnover

Abstract Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature and the slow turnover of NPC components complicates investigations of how individual nucleoporins act in these diverse processes. To address this question, we apply an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins NUP153, NUP50 and TPR. Acute depletion of TPR causes rapid and pronounced changes in transcriptomic profiles. These changes are dissimilar to shifts observed after loss of NUP153 or NUP50, but closely related to changes caused by depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) to NPCs and results in abnormal RNA transcription and export. Our findings demonstrate a unique and pivotal role of TPR in gene expression through TREX-2- and/or NXF1-dependent mRNA turnover.

scholarly journals The Role of Nucleoporin Elys in Nuclear Pore Complex Assembly and Regulation of Genome Architecture

2020 ◽  
Vol 21 (24) ◽  
pp. 9475
Author(s):  
Yuri Y. Shevelyov
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Pore Complex ◽  
Nuclear Lamina ◽  
Nuclear Pore ◽  
Genome Architecture ◽  
Nuclear Pore Complexes ◽  
Current State ◽  
Long Time ◽  
Pore Complexes

For a long time, the nuclear lamina was thought to be the sole scaffold for the attachment of chromosomes to the nuclear envelope (NE) in metazoans. However, accumulating evidence indicates that nuclear pore complexes (NPCs) comprised of nucleoporins (Nups) participate in this process as well. One of the Nups, Elys, initiates NPC reassembly at the end of mitosis. Elys directly binds the decondensing chromatin and interacts with the Nup107–160 subcomplex of NPCs, thus serving as a seeding point for the subsequent recruitment of other NPC subcomplexes and connecting chromatin with the re-forming NE. Recent studies also uncovered the important functions of Elys during interphase where it interacts with chromatin and affects its compactness. Therefore, Elys seems to be one of the key Nups regulating chromatin organization. This review summarizes the current state of our knowledge about the participation of Elys in the post-mitotic NPC reassembly as well as the role that Elys and other Nups play in the maintenance of genome architecture.

scholarly journals CRM1 promotes capsid disassembly and nuclear envelope translocation of adenovirus independently of its export function

2021 ◽  
Author(s):  
Floriane Lagadec ◽  
Irene Carlon-Andres ◽  
Jessica Ragues ◽  
Sarah Port ◽  
Harald Wodrich ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Microtubule Organizing Center ◽  
Leptomycin B ◽  
Pore Complexes ◽  
Nuclear Export Receptor ◽  
Mitotic Cells ◽  
Capsid Disassembly

After receptor-mediated endocytosis and endosomal escape, adenoviral capsids can travel via microtubule organizing centers to the nuclear envelope. Upon capsid disassembly, viral genome import into nuclei of interphase cells then occurs through nuclear pore complexes, involving the nucleoporins Nup214 and Nup358. Import also requires the activity of the classic nuclear export receptor CRM1, as it is blocked by the selective inhibitor leptomycin B. We have now used artificially enucleated as well as mitotic cells to analyze the role of an intact nucleus in different steps of the viral life cycle. In enucleated U2OS cells, viral capsids traveled to the microtubule organizing center, whereas their removal from this complex was blocked, suggesting that this step required nuclear factors. In mitotic cells, on the other hand, CRM1 promoted capsid disassembly and genome release, suggesting a role of this protein that does not require intact nuclear envelopes or nuclear pore complexes and is distinct from its function as a nuclear export receptor. Similar to enucleation, inhibition of CRM1 by leptomycin B also leads to an arrest of adenoviral capsids at the microtubule organizing center. In a small-scale screen using leptomycin B-resistant versions of CRM1, we identified a mutant, CRM1 W142A P143A, that is compromised with respect to adenoviral capsid disassembly, both in interphase and in mitotic cells. Strikingly, this mutant is capable of exporting cargo proteins out of the nucleus of living cells or digitonin-permeabilized cells, pointing to a role of the mutated region that is not directly linked to nuclear export. IMPORTANCE A role of nucleoporins and of soluble transport factors in adenoviral genome import into the nucleus of infected cells in interphase has previously been established. The nuclear export receptor CRM1 promotes genome import, but its precise function is not known. Using enucleated and mitotic cells, we showed that CRM1 does not simply function by exporting a crucial factor out of the nucleus that would then trigger capsid disassembly and genome import. Instead, CRM1 has an export-independent role, a notion that is also supported by a mutant, CRM1 W142A P143A, which is export-competent but deficient in viral capsid disassembly, both in interphase and in mitotic cells.

scholarly journals Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Annina Denoth-Lippuner ◽  
Marek Konrad Krzyzanowski ◽  
Catherine Stober ◽  
Yves Barral
Keyword(s):  
Mother Cell ◽  
Nuclear Organization ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Saga Complex ◽  
Chromosomal Dna ◽  
Pore Complexes ◽  
Chromosomal Recombination

In eukaryotes, intra-chromosomal recombination generates DNA circles, but little is known about how cells react to them. In yeast, partitioning of such circles to the mother cell at mitosis ensures their loss from the population but promotes replicative ageing. Nevertheless, the mechanisms of partitioning are debated. In this study, we show that the SAGA complex mediates the interaction of non-chromosomal DNA circles with nuclear pore complexes (NPCs) and thereby promotes their confinement in the mother cell. Reciprocally, this causes retention and accumulation of NPCs, which affects the organization of ageing nuclei. Thus, SAGA prevents the spreading of DNA circles by linking them to NPCs, but unavoidably causes accumulation of circles and NPCs in the mother cell, and thereby promotes ageing. Together, our data provide a unifying model for the asymmetric segregation of DNA circles and how age affects nuclear organization.

scholarly journals TORC1 inactivation stimulates autophagy of nucleoporin and nuclear pore complexes

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Yui Tomioka ◽  
Tetsuya Kotani ◽  
Hiromi Kirisako ◽  
Yu Oikawa ◽  
Yayoi Kimura ◽  
...  
Keyword(s):  
Membrane Vesicles ◽  
Specific Factor ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Binding Ability ◽  
Yeast Saccharomyces Cerevisiae ◽  
Selective Autophagy ◽  
Tor Kinase ◽  
Autophagic Degradation ◽  
Pore Complexes

The mechanisms underlying turnover of the nuclear pore complex (NPC) and the component nucleoporins (Nups) are still poorly understood. In this study, we found that the budding yeast Saccharomyces cerevisiae triggers NPC degradation by autophagy upon the inactivation of Tor kinase complex 1. This degradation largely depends on the selective autophagy-specific factor Atg11 and the autophagy receptor–binding ability of Atg8, suggesting that the NPC is degraded via receptor-dependent selective autophagy. Immunoelectron microscopy revealed that NPCs embedded in nuclear envelope–derived double-membrane vesicles are sequestered within autophagosomes. At least two pathways are involved in NPC degradation: Atg39-dependent nucleophagy (selective autophagy of the nucleus) and a pathway involving an unknown receptor. In addition, we found the interaction between Nup159 and Atg8 via the Atg8-family interacting motif is important for degradation of this nucleoporin not assembled into the NPC. Thus, this study provides the first evidence for autophagic degradation of the NPC and Nups, which we term “NPC-phagy” and “nucleoporinophagy.”

scholarly journals Evidence for a Posttranscriptional Role of a TFIIICα-like Protein in Chironomus tentans

2002 ◽  
Vol 13 (5) ◽  
pp. 1765-1777 ◽  
Author(s):  
Nafiseh Sabri ◽  
Ann-Kristin Östlund Farrants ◽  
Ulf Hellman ◽  
Neus Visa
Keyword(s):  
Molecular Mass ◽  
Transcription Initiation ◽  
Large Fraction ◽  
Gel Filtration ◽  
Nuclear Pore ◽  
Chironomus Tentans ◽  
Nuclear Pore Complexes ◽  
Α Subunit ◽  
Pore Complexes

We have cloned and sequenced a cDNA that encodes for a nuclear protein of 238 kDa in the dipteran Chironomus tentans. This protein, that we call p2D10, is structurally similar to the α subunit of the general transcription factor TFIIIC. Using immunoelectron microscopy we have shown that a fraction of p2D10 is located at sites of transcription, which is consistent with a possible role of this protein in transcription initiation. We have also found that a large fraction of p2D10 is located in the nucleoplasm and in the nuclear pore complexes. Using gel filtration chromatography and coimmunoprecipitation methods, we have identified and characterized two p2D10-containing complexes that differ in molecular mass and composition. The heavy p2D10-containing complex contains at least one other component of the TFIIIC complex, TFIIIC-ε. Based on its molecular mass and composition, the heavy p2D10-containing complex may be the Pol III holoenzyme. The light p2D10-containing complex contains RNA together with at least two proteins that are thought to be involved in mRNA trafficking, RAE1 and hrp65. The observations reported here suggest that this new TFIIIC-α-like protein is involved in posttranscriptional steps of premRNA metabolism in Chironomus tentans.

scholarly journals Integrity of the short arm of nuclear pore Y-complex is required for mouse embryonic stem cell growth and differentiation

2020 ◽  
Author(s):  
Alba Gonzalez-Estevez ◽  
Annalisa Verrico ◽  
Clarisse Orniacki ◽  
Bernardo Reina-San-Martin ◽  
Valérie Doye
Keyword(s):  
Cell Growth ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Proliferation And Differentiation ◽  
Mild Reduction ◽  
Cell Growth And Differentiation ◽  
Pore Complexes

SUMMARYNuclear pore complexes (NPCs) are established players in cell division and differentiation. However studies on the contribution of individual NPC subunits to these processes are still scarce. Here we use mouse embryonic stem cells (mESCs) to characterize the role of NPC structural components, focusing on the short arm of the Y-complex that comprises Nup85, Seh1 and Nup43. We show that Seh1 and Nup43, although dispensable at the pluripotent stage, are required for normal cell growth rates, and for mESC viability upon differentiation. mESCs lacking Seh1 or Nup43 display a mild reduction of NPC density that is also observed in an N-terminally truncated Nup85 mutant in which interaction with Seh1 is greatly impaired. However, mESC proliferation and differentiation are not altered in these Nup85 mutant cells, indicating that it is the integrity of the Y-complex, rather than the number of NPCs, that is critical to ensure these processes.

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