scholarly journals Enhanced nuclear protein export in premature aging and rescue of the progeria phenotype by modulation of CRM1 activity

Aging Cell ◽  
2019 ◽  
Vol 18 (5) ◽  
Author(s):  
Ian García‐Aguirre ◽  
Alma Alamillo‐Iniesta ◽  
Ruth Rodríguez‐Pérez ◽  
Griselda Vélez‐Aguilera ◽  
Elianeth Amaro‐Encarnación ◽  
...  
Keyword(s):  
Nuclear Protein ◽  
Protein Export ◽  
Premature Aging

Evidence for a Role of CRM1 in Signal-Mediated Nuclear Protein Export

Science ◽  
1997 ◽  
Vol 278 (5335) ◽  
pp. 141-144 ◽  
Author(s):  
Batool Ossareh-Nazari ◽  
Françoise Bachelerie ◽  
Catherine Dargemont
Keyword(s):  
Nuclear Protein ◽  
Protein Export

scholarly journals Reconstitution of nuclear protein export in isolated nuclear envelopes

2002 ◽  
Vol 158 (5) ◽  
pp. 849-854 ◽  
Author(s):  
Jan Peter Siebrasse ◽  
Elias Coutavas ◽  
Reiner Peters
Keyword(s):  
Protein Kinase ◽  
Nuclear Export ◽  
Xenopus Oocytes ◽  
Nuclear Protein ◽  
Nuclear Export Signal ◽  
Protein Export ◽  
Leptomycin B ◽  
Permeabilized Cells ◽  
Export Signal ◽  
Kinase A

Signal-dependent nuclear protein export was studied in perforated nuclei and isolated nuclear envelopes of Xenopus oocytes by optical single transporter recording. Manually isolated and purified oocyte nuclei were attached to isoporous filters and made permeable for macromolecules by perforation. Export of a recombinant protein (GG-NES) containing the nuclear export signal (NES) of the protein kinase A inhibitor through nuclear envelope patches spanning filter pores could be induced by the addition of GTP alone. Export continued against a concentration gradient, and was NES dependent and inhibited by leptomycin B and GTPγS, a nonhydrolyzable GTP analogue. Addition of recombinant RanBP3, a potential cofactor of CRM1-dependent export, did not promote GG-NES export at stoichiometric concentration but gradually inhibited export at higher concentrations. In isolated filter-attached nuclear envelopes, export of GG-NES was virtually abolished in the presence of GTP alone. However, a preformed export complex consisting of GG-NES, recombinant human CRM1, and RanGTP was rapidly exported. Unexpectedly, export was strongly reduced when the export complex contained RanGTPγS or RanG19V/Q69L-GTP, a GTPase-deficient Ran mutant. This paper shows that nuclear transport, previously studied in intact and permeabilized cells only, can be quantitatively analyzed in perforated nuclei and isolated nuclear envelopes.

scholarly journals The nucleoporin-like protein NLP1 (hCG1) promotes CRM1-dependent nuclear protein export

2012 ◽  
Vol 125 (1) ◽  
pp. 144-154 ◽  
Author(s):  
I. Waldmann ◽  
C. Spillner ◽  
R. H. Kehlenbach
Keyword(s):  
Nuclear Protein ◽  
Protein Export

scholarly journals Optogenetic control of nuclear protein export

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Dominik Niopek ◽  
Pierre Wehler ◽  
Julia Roensch ◽  
Roland Eils ◽  
Barbara Di Ventura
Keyword(s):  
Nuclear Protein ◽  
Protein Export ◽  
Optogenetic Control

Histones To The Cytosol: Role Of Nuclear Protein Export In Erythroid Nuclear Condensation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 310-310
Author(s):  
Amalia A Figueroa ◽  
Srividhya Venkatesan ◽  
Shilpa M Hattangadi
Keyword(s):  
Nuclear Export ◽  
Cell Biology ◽  
Nuclear Protein ◽  
Fetal Liver ◽  
Chromatin Condensation ◽  
Protein Export ◽  
Basic Knowledge ◽  
High Morbidity ◽  
Nuclear Condensation ◽  
Primary Mouse

Abstract Erythropoietin-refractory anemias and red cell aplasias are rare but devastating disorders in children, with no known treatment other than chronic transfusions and bone marrow transplant, with high morbidity and mortality. New, improved treatments for such anemias are severely limited by incomplete understanding of critical terminal erythroid processes such as enucleation. Our long-term goal is to understand the regulation of erythroid nuclear condensation culminating in enucleation in order to increase our basic knowledge of important cell biology concepts like nuclear export and nuclear condensation during erythropoiesis and ultimately help optimize new treatments for anemia. Proteomic examination of normal pycnotic nuclei from mouse fetal liver (definitive adult erythropoiesis) revealed a striking decrease in almost all nuclear proteins, suggesting that nuclear protein export occurs prior to extrusion. Expression of the nuclear exportin, Exportin 7 (Xpo7) is highly erythroid-specific—utilizing a tightly-regulated erythroid-specific promoter, induced during erythropoiesis, and abundant in late erythroblasts. Knockdown of Xpo7 in primary mouse fetal liver erythroblasts resulted in severe disruption of chromatin condensation and enucleation but otherwise had little effect on erythroid differentiation, including hemoglobin accumulation (manuscript submitted), suggesting that protein export is crucial to the process of nuclear condensation. Nuclei in Xpo7 knockdown cells were larger and less dense than controls. Strikingly, DNA binding proteins such as histones H2A and H3 accumulated in the cytoplasm of normal late erythroblasts prior to and during enucleation, but not in cells lacking Xpo7. We have confirmed by chromatin immunoprecipitation and RACE-PCR that there is an erythroid-specific promoter (and start-site) for Xpo7, whose expression is not conserved in lower vertebrates or in primitive mouse erythroblasts. We hypothesize that the erythroid-specific function of Xpo7 therefore may account for the fact that red cells are not enucleated in these other biological systems. We have also performedimmunoprecipitation on the erythroid and non-erythroid forms of Xpo7 and determined several erythroid-specific cargo proteins of Xpo7 that are involved with other types of chromatin condensation (including Rcc1 which is involved in chromosome condensation). We are starting to build a model for how Xpo7 facilitates the removal and replacement of histones in the erythroblast nucleus in order to allow adequate nuclear condensation for extrusion. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Mobile FG Nucleoporin Nup98 Is a Cofactor for Crm1-dependent Protein Export

2010 ◽  
Vol 21 (11) ◽  
pp. 1885-1896 ◽  
Author(s):  
Masahiro Oka ◽  
Munehiro Asally ◽  
Yoshinari Yasuda ◽  
Yutaka Ogawa ◽  
Taro Tachibana ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Nuclear Protein ◽  
Mutational Analysis ◽  
Specific Inhibitor ◽  
Protein Export ◽  
Dependent Manner ◽  
Repeat Region ◽  
Leptomycin B ◽  
Dependent Protein ◽  
Nuclear Export Receptor

Nup98 is a mobile nucleoporin that forms distinct dots in the nucleus, and, although a role for Nup98 in nuclear transport has been suggested, its precise function remains unclear. Here, we show that Nup98 plays an important role in Crm1-mediated nuclear protein export. Nuclear, but not cytoplasmic, dots of EGFP-tagged Nup98 disappeared rapidly after cell treatment with leptomycin B, a specific inhibitor of the nuclear export receptor, Crm1. Mutational analysis demonstrated that Nup98 physically and functionally interacts with Crm1 in a RanGTP-dependent manner through its N-terminal phenylalanine-glycine (FG) repeat region. Moreover, the activity of the Nup98-Crm1 complex was modulated by RanBP3, a known cofactor for Crm1-mediated nuclear export. Finally, cytoplasmic microinjection of anti-Nup98 inhibited the Crm1-dependent nuclear export of proteins, concomitant with the accumulation of anti-Nup98 in the nucleus. These results clearly demonstrate that Nup98 functions as a novel shuttling cofactor for Crm1-mediated nuclear export in conjunction with RanBP3.

scholarly journals A subset of FG-nucleoporins is necessary for efficient Msn5-mediated nuclear protein export

2013 ◽  
Vol 1833 (5) ◽  
pp. 1096-1103 ◽  
Author(s):  
Erin M. Finn ◽  
Elise P. DeRoo ◽  
George W. Clement ◽  
Sheila Rao ◽  
Sarah E. Kruse ◽  
...  
Keyword(s):  
Nuclear Protein ◽  
Protein Export

scholarly journals Identification of an NTF2-Related Factor That Binds Ran-GTP and Regulates Nuclear Protein Export

1999 ◽  
Vol 19 (12) ◽  
pp. 8616-8624 ◽  
Author(s):  
Ben E. Black ◽  
Lyne Lévesque ◽  
James M. Holaska ◽  
Todd C. Wood ◽  
Bryce M. Paschal
Keyword(s):  
Mammalian Cells ◽  
Nuclear Protein ◽  
Direct Interaction ◽  
Effector Proteins ◽  
Protein Export ◽  
Nuclear Pore ◽  
Related Factor ◽  
Transport Reaction ◽  
Ran Gtp

ABSTRACT Active transport of macromolecules between the nucleus and cytoplasm requires signals for import and export and their recognition by shuttling receptors. Each class of macromolecule is thought to have a distinct receptor that mediates the transport reaction. Assembly and disassembly reactions of receptor-substrate complexes are coordinated by Ran, a GTP-binding protein whose nucleotide state is regulated catalytically by effector proteins. Ran function is modulated in a noncatalytic fashion by NTF2, a protein that mediates nuclear import of Ran-GDP. Here we characterize a novel component of the Ran system that is 26% identical to NTF2, which based on its function we refer to as NTF2-related export protein 1 (NXT1). In contrast to NTF2, NXT1 preferentially binds Ran-GTP, and it colocalizes with the nuclear pore complex (NPC) in mammalian cells. These properties, together with the fact that NXT1 shuttles between the nucleus and the cytoplasm, suggest an active role in nuclear transport. Indeed, NXT1 stimulates nuclear protein export of the NES-containing protein PKI in vitro. The export function of NXT1 is blocked by the addition of leptomycin B, a compound that selectively inhibits the NES receptor Crm1. Thus, NXT1 regulates the Crm1-dependent export pathway through its direct interaction with Ran-GTP.

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