Stress eating: Autophagy targets nuclear pore complexes

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.

Download Full-text

Tts1, the fission yeast homologue of the TMEM33 family, functions in NE remodeling during mitosis

Molecular Biology of the Cell ◽

10.1091/mbc.e13-12-0729 ◽

2014 ◽

Vol 25 (19) ◽

pp. 2970-2983 ◽

Cited By ~ 22

Author(s):

Dan Zhang ◽

Snezhana Oliferenko

Keyword(s):

Fission Yeast ◽

Structural Features ◽

Spindle Pole ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

C Terminus ◽

Spindle Pole Bodies ◽

Evolutionarily Conserved ◽

Pore Complexes ◽

Insight Into

The fission yeast Schizosaccharomyces pombe undergoes “closed” mitosis in which the nuclear envelope (NE) stays intact throughout chromosome segregation. Here we show that Tts1, the fission yeast TMEM33 protein that was previously implicated in organizing the peripheral endoplasmic reticulum (ER), also functions in remodeling the NE during mitosis. Tts1 promotes insertion of spindle pole bodies (SPBs) in the NE at the onset of mitosis and modulates distribution of the nuclear pore complexes (NPCs) during mitotic NE expansion. Structural features that drive partitioning of Tts1 to the high-curvature ER domains are crucial for both aspects of its function. An amphipathic helix located at the C-terminus of Tts1 is important for ER shaping and modulating the mitotic NPC distribution. Of interest, the evolutionarily conserved residues at the luminal interface of the third transmembrane region function specifically in promoting SPB-NE insertion. Our data illuminate cellular requirements for remodeling the NE during “closed” nuclear division and provide insight into the structure and functions of the eukaryotic TMEM33 family.

Download Full-text

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

Download Full-text

TORC1 inactivation stimulates autophagy of nucleoporin and nuclear pore complexes

The Journal of Cell Biology ◽

10.1083/jcb.201910063 ◽

2020 ◽

Vol 219 (7) ◽

Cited By ~ 6

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.”

Download Full-text

Nup2 requires a highly divergent partner, NupA, to fulfill functions at nuclear pore complexes and the mitotic chromatin region

Molecular Biology of the Cell ◽

10.1091/mbc.e14-09-1359 ◽

2015 ◽

Vol 26 (4) ◽

pp. 605-621 ◽

Cited By ~ 13

Author(s):

Sarine Markossian ◽

Subbulakshmi Suresh ◽

Aysha H. Osmani ◽

Stephen A. Osmani

Keyword(s):

Spindle Assembly Checkpoint ◽

Ectopic Expression ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Chromatin Region ◽

Mitotic Kinase ◽

Pore Complexes ◽

Surveillance Mechanism ◽

Insight Into ◽

Mitotic Chromatin

Chromatin and nuclear pore complexes (NPCs) undergo dramatic changes during mitosis, which in vertebrates and Aspergillus nidulans involves movement of Nup2 from NPCs to the chromatin region to fulfill unknown functions. This transition is shown to require the Cdk1 mitotic kinase and be promoted prematurely by ectopic expression of the NIMA kinase. Nup2 localizes with a copurifying partner termed NupA, a highly divergent yet essential NPC protein. NupA and Nup2 locate throughout the chromatin region during prophase but during anaphase move to surround segregating DNA. NupA function is shown to involve targeting Nup2 to its interphase and mitotic locations. Deletion of either Nup2 or NupA causes identical mitotic defects that initiate a spindle assembly checkpoint (SAC)–dependent mitotic delay and also cause defects in karyokinesis. These mitotic problems are not caused by overall defects in mitotic NPC disassembly–reassembly or general nuclear import. However, without Nup2 or NupA, although the SAC protein Mad1 locates to its mitotic locations, it fails to locate to NPCs normally in G1 after mitosis. Collectively the study provides new insight into the roles of Nup2 and NupA during mitosis and in a surveillance mechanism that regulates nucleokinesis when mitotic defects occur after SAC fulfillment.

Download Full-text

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

Download Full-text

Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9

eLife ◽

10.7554/elife.18825 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 15

Author(s):

Juliana S Capitanio ◽

Ben Montpetit ◽

Richard W Wozniak

Keyword(s):

In Vitro Assays ◽

Nuclear Pore ◽

Nuclear Pore Complexes ◽

Rna Helicases ◽

Binding Partner ◽

Binding Partners ◽

Pore Complexes ◽

Insight Into ◽

Similar Gene

Beyond their role at nuclear pore complexes, some nucleoporins function in the nucleoplasm. One such nucleoporin, Nup98, binds chromatin and regulates gene expression. To gain insight into how Nup98 contributes to this process, we focused on identifying novel binding partners and understanding the significance of these interactions. Here we report on the identification of the DExH/D-box helicase DHX9 as an intranuclear Nup98 binding partner. Various results, including in vitro assays, show that the FG/GLFG region of Nup98 binds to N- and C-terminal regions of DHX9 in an RNA facilitated manner. Importantly, binding of Nup98 stimulates the ATPase activity of DHX9, and a transcriptional reporter assay suggests Nup98 supports DHX9-stimulated transcription. Consistent with these observations, our analysis revealed that Nup98 and DHX9 bind interdependently to similar gene loci and their transcripts. Based on our results, we propose that Nup98 functions as a co-factor that regulates DHX9 and, potentially, other RNA helicases.

Download Full-text

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.

Download Full-text