Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Karyopherin enrichment and compensation fortifies the nuclear pore complex against nucleocytoplasmic leakage

ABSTRACT: Nuclear pore complexes (NPCs) discriminate non-specific macromolecules from importin and exportin receptors, collectively termed karyopherins (Kaps), that mediate nucleocytoplasmic transport. This selective barrier function is attributed to the behavior of intrinsically disordered phenylalanine-glycine nucleoporins (FG Nups) that guard the NPC channel. However, NPCs in vivo are typically enriched with different Kaps, and how they impact on the NPC barrier remains unknown. Here, we show that two major Kaps, importinβ1/karyopherinβ1 (Kapβ1) and exportin 1/chromosomal maintenance 1 (CRM1) are required to fortify NPC barrier function in vivo. Their enrichment at the NPC is sustained by promiscuous binding interactions with the FG Nups resulting in a compensatory mechanism that is constrained by their respective cellular abundances and different binding kinetics as evidenced for another Kap, Importin-5. Hence, Kapβ1 and CRM1 engage in a balancing act to reinforce NPC barrier function. Consequently, NPC malfunction and nucleocytoplasmic leakage result from poor Kap enrichment.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF

ORGANISM(S): Canis Familiaris (dog) (canis Lupus Familiaris)

TISSUE(S): Cell Culture

SUBMITTER: Alexander Schmidt

LAB HEAD: Alexander Schmidt

PROVIDER: PXD028074 | Pride | 2022-01-26

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	001_2E-siRNA_D19.raw	Raw
	001_JK-KapB1_PRM_C21.raw	Raw
	002_2E-siRNA_D19.raw	Raw
	002_JK-KapB1_PRM_C21.raw	Raw
	003_2E-siRNA_D19.raw	Raw

Items per page:

1 - 5 of 34

Similar Datasets

Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore

Project description:Non-centrosomal microtubule organizing centers (MTOCs) are important for microtubule organization in many cell types. In fission yeast Schizosaccharomyces pombe, the protein Mto1, together with partner protein Mto2 (Mto1/2 complex), recruits the g-tubulin complex to multiple non-centrosomal MTOCs, including the nuclear envelope (NE). Here, we develop a comparative-interactome mass spectrometry approach to determine how Mto1 localizes to the NE. Surprisingly, we find that Mto1, a constitutively cytoplasmic protein, docks at nuclear pore complexes (NPCs), via interaction with exportin Crm1 and cytoplasmic FG-nucleoporin Nup146. Although Mto1 is not a nuclear export cargo, it binds Crm1 via a nuclear export signal-like sequence, and docking requires both Ran in the GTP-bound state and Nup146 FG repeats. In addition to determining the mechanism of MTOC formation at the NE, our results reveal a novel role for Crm1 and the nuclear export machinery in the stable docking of a cytoplasmic protein complex at NPCs.

2018-05-22 | PXD008334 | Pride

Selective autophagy degrades nuclear pore complexes

Project description:Nuclear pore complexes (NPCs) are giant cylindrical structures embedded into the nuclear envelope and mediate nucleocytoplasmic exchange. NPC longevity has been linked to aging but since they appear to rarely turn over, the underlying mechanisms remain understudied. Here, we show that upon nitrogen starvation and genetic interference with NPC architecture, Nups are rapidly degraded in budding yeast. We demonstrate that NPC turnover involves 25 vacuolar proteases and the core autophagic machinery. Autophagic degradation is mediated by the cytoplasmically exposed Nup159 that serves as intrinsic cargo receptor and directly binds to the autophagic marker protein Atg8. The inducible manner of this mechanism might explain why NPCs are long-lived under specific conditions

2019-11-13 | PXD011571 | Pride

Distinct Basket Nucleoporins roles in Nuclear Pore Function and Gene Expression

Project description: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 used an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins Nup153, Nup50 and Tpr. Here, we provide MS data for the Nuclear Pore-enriched fraction of human DLD-1 cells, expressing CRISPR-engeneered degron, fused with the endogenous locus of corresponding basket NUPs, in the absence or presence of Auxin.

2020-06-30 | PXD020075 | Pride

Pre-assembled Nuclear Pores Insert into the Nuclear Envelope During Early Development

Project description:Nuclear Pore Complexes (NPCs) span the nuclear envelope (NE) and mediate nucleocytoplasmic transport. In metazoan oocytes and early embryos, NPCs not only reside within the NE but also at some endoplasmatic reticulum (ER) membrane sheets, termed annulate lamellae (AL). Although a role for AL as NPC storage pools has been discussed, it remains controversial if and how they contribute to the NPC density at the NE. Here we show that AL insert into the NE as the ER feeds rapid nuclear expansion in Drosophila blastoderm embryos. We demonstrate that NPCs within AL resemble pore scaffolds that mature only upon insertion into the NE. We delineate a topological model in which NE openings are critical for AL uptake that nevertheless occurs without compromising the permeability barrier of the NE. We finally show that this unanticipated mode of pore insertion is developmentally regulated and operates prior to gastrulation.

2016-07-12 | PXD004120 | Pride

Genome organization regulates nuclear pore complex formation and promotes differentiation during Drosophila oogenesis [RNA-seq]

Project description:Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ-cell genes during differentiation and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we find that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ-cell genes into a silenced state and activating a group of oocyte genes and Nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, crosstalk between genome architecture and NPCs is essential for successful cell fate transitions.

2024-05-29 | GSE248057 | GEO

Genome organization regulates nuclear pore complex formation and promotes differentiation during Drosophila oogenesis [CUT&RUN]

Project description:Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in Genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ-cell genes during differentiation and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we find that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ-cell genes into a silenced state and activating a group of oocyte genes and Nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, crosstalk between genome architecture and NPCs is essential for successful cell fate transitions.

2024-05-29 | GSE250350 | GEO

Genome organization regulates nuclear pore complex formation and promotes differentiation during Drosophila oogenesis [RNA-Seq2]

2024-05-29 | GSE267732 | GEO

SILAC-Tp (12 importins) - Extensive cargo identification reveals distinct biological roles of the 12 importin pathways

Project description:Importin-beta family proteins are nucleocytoplasmic transport receptors (NTRs), and they transport most nuclear proteins as their cargoes into and out of the nuclei. Human cells have 20 species of importin-beta family NTRs, of which 10 (importin-beta, transportin-1, -2, -SR, importin-4, -5, -7, -8, -9, and -11) are nuclear import receptors and 2 (importin-13, and exportin-4) are bi-directional receptors. Here, we identified the import cargo proteins of these 12 NTRs by a method called SILAC-Tp, which employs stable isotope labeling with amino acids in cell culture (SILAC), an in vitro reconstituted transport system, and LC-MS/MS.

2017-01-20 | PXD004655 | Pride

SILAC-Tp (12 importins)

2017-03-30 | MSV000080815 | MassIVE

Nuclear transport surveillance of p53 by nuclear pores in glioblastoma

Project description:Nuclear pore complexes (NPCs) are the central apparatus of nucleocytoplasmic transport. Disease-specific alterations of NPCs contribute to the pathogenesis of many cancers; however, the roles of NPCs in glioblastoma (GBM) are unknown. In this study, we report genomic amplification of NUP107, a component of NPCs, in GBM and show that NUP107 is overexpressed simultaneously with MDM2, a critical E3 ligase that mediates p53 degradation. Depletion of NUP107 inhibits the growth of GBM cell lines through p53 protein stabilization. Mechanistically, NPCs establish a p53 degradation platform via an export pathway coupled with 26S proteasome tethering. NUP107 is the keystone for NPC assembly; the loss of NUP107 affects the integrity of the NPC structure, and thus the proportion of 26S proteasome in the vicinity of nuclear pores significantly decreases. Together, our findings establish roles of NPCs in transport surveillance and provide insights into p53 inactivation in GBM.

2023-08-19 | GSE216888 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data