TORC1 inactivation stimulates autophagy of nucleoporin and nuclear 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.”

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Nuclear Envelope Dynamics During Mitosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100103188 ◽

1988 ◽

Vol 46 ◽

pp. 224-225

Author(s):

Brian Burke

Keyword(s):

Nuclear Envelope ◽

Membrane Vesicles ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Animal Cells ◽

Interphase Chromosome ◽

Lamin B ◽

Chromosome Architecture ◽

Complex Membrane ◽

Pore Complexes

The nuclear envelope is a complex membrane structure that forms the boundary of the nuclear compartment in eukaryotes. It regulates the passage of macromolecules between the two compartments and may be important for organizing interphase chromosome architecture. In interphase animal cells it forms a remarkably stable structure consisting of a double membrane ouerlying a protein meshwork or lamina and penetrated by nuclear pore complexes. The latter form the channels for nucleocytoplasmic exchange of macromolecules, At the onset of mitosis, however, it rapidly disassembles, the membranes fragment to yield small vesicles and the lamina, which is composed of predominantly three polypeptides, lamins R, B and C (MW approx. 74, 68 and 65 kDa respectiuely), breaks down. Lamins B and C are dispersed as monomers throughout the mitotic cytoplasm, while lamin B remains associated with the nuclear membrane vesicles.

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Nucleocytoplasmic transport of macromolecules

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.61.2.193-211.1997 ◽

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.

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NPC-phagy: selective autophagy of the nuclear pore complexes

Autophagy ◽

10.1080/15548627.2020.1798199 ◽

2020 ◽

Vol 16 (10) ◽

pp. 1735-1736

Author(s):

Zhangyuan Yin ◽

Daniel J. Klionsky

Keyword(s):

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Selective Autophagy ◽

Pore Complexes

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Nucleophagy—Implications for Microautophagy and Health

International Journal of Molecular Sciences ◽

10.3390/ijms21124506 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4506 ◽

Cited By ~ 3

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.

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Inheritance of yeast nuclear pore complexes requires the Nsp1p subcomplex

The Journal of Cell Biology ◽

10.1083/jcb.201304047 ◽

2013 ◽

Vol 203 (2) ◽

pp. 187-196 ◽

Cited By ~ 28

Author(s):

Tadashi Makio ◽

Diego L. Lapetina ◽

Richard W. Wozniak

Keyword(s):

Daughter Cell ◽

Selection Process ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Yeast Saccharomyces Cerevisiae ◽

Macromolecular Complexes ◽

Daughter Cells ◽

Bud Neck ◽

Pore Complexes ◽

Mother Nucleus

In the yeast Saccharomyces cerevisiae, organelles and macromolecular complexes are delivered from the mother to the emerging daughter during cell division, thereby ensuring progeny viability. Here, we have shown that during mitosis nuclear pore complexes (NPCs) in the mother nucleus are actively delivered through the bud neck and into the daughter cell concomitantly with the nuclear envelope. Furthermore, we show that NPC movement into the daughter cell requires members of an NPC subcomplex containing Nsp1p and its interacting partners. NPCs lacking these nucleoporins (Nups) were blocked from entry into the daughter by a putative barrier at the bud neck. This selection process could be observed within individual cells such that NPCs containing Nup82p (an Nsp1p-interacting Nup) were transferred to the daughter cells while functionally compromised NPCs lacking Nup82p were retained in the mother. This mechanism is proposed to facilitate the inheritance of functional NPCs by daughter cells.

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Stress eating: Autophagy targets nuclear pore complexes

The Journal of Cell Biology ◽

10.1083/jcb.202006007 ◽

2020 ◽

Vol 219 (7) ◽

Author(s):

Angelina Sarah Gross ◽

Martin Graef

Keyword(s):

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Selective Autophagy ◽

Stress Eating ◽

Pore Complexes ◽

Insight Into

Lee et al. (2020. Nat. Cell Biol.https://doi.org/10.1038/s41556-019-0459-2) and, in this issue, Tomioka et al. (2020. J. Cell Biol.https://doi.org/10.1083/jcb.201910063) describe the targeted degradation of nuclear pore complexes (NPCs) by selective autophagy, providing insight into the mechanisms of turnover for individual nucleoporins and entire NPCs.

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Selective autophagy degrades nuclear pore complexes

Nature Cell Biology ◽

10.1038/s41556-019-0459-2 ◽

2020 ◽

Vol 22 (2) ◽

pp. 159-166 ◽

Cited By ~ 19

Author(s):

Chia-Wei Lee ◽

Florian Wilfling ◽

Paolo Ronchi ◽

Matteo Allegretti ◽

Shyamal Mosalaganti ◽

...

Keyword(s):

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Selective Autophagy ◽

Pore Complexes

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The dynamic three-dimensional organization of the diploid yeast genome

eLife ◽

10.7554/elife.23623 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 28

Author(s):

Seungsoo Kim ◽

Ivan Liachko ◽

Donna G Brickner ◽

Kate Cook ◽

William S Noble ◽

...

Keyword(s):

Nuclear Periphery ◽

Three Dimensional ◽

Culture Conditions ◽

Yeast Genome ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Yeast Saccharomyces Cerevisiae ◽

Chromosome Conformation ◽

Homolog Pairing ◽

Pore Complexes

The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. However, even in this well-studied model, it is unclear how homolog pairing in diploids or environmental conditions influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid yeasts. After controlling for the Rabl-like orientation using a polymer model, we observe significant homolog proximity that increases in saturated culture conditions. Surprisingly, we observe a localized increase in homologous interactions between the HAS1-TDA1 alleles specifically under galactose induction and saturated growth. This pairing is accompanied by relocalization to the nuclear periphery and requires Nup2, suggesting a role for nuclear pore complexes. Together, these results reveal that the diploid yeast genome has a dynamic and complex 3D organization.

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