PXD015656 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | C9orf72 arginine-rich dipeptide repeat proteins disrupt importin beta-mediated nuclear import |
Description | Disruption of nucleocytoplasmic transport (NCT), including mislocalization of the importin beta cargo, TDP-43, is a hallmark of amyotrophic lateral sclerosis (ALS), including ALS caused by a hexanucleotide repeat expansion in C9orf72. However, the mechanism(s) remain unclear. Importin beta and its cargo adaptors have been shown to co-precipitate with the C9orf72-arginine-containing dipeptide repeat proteins (R-DPRs), poly-glycine arginine (GR) and poly-proline arginine (PR), and are protective in genetic modifier screens. Here, we show that R-DPRs interact with importin beta, disrupt its cargo loading, and inhibit nuclear import in permeabilized mouse neurons and HeLa cells, in a manner that can be rescued by RNA. Although R-DPRs induce widespread protein aggregation in this in vitro system, transport disruption is not due to NCT protein sequestration, nor blockade of the phenylalanine-glycine (FG)-rich nuclear pore complex. Our results support a model in which R-DPRs interfere with nuclear transport receptors in the vicinity of the nuclear envelope. |
HostingRepository | PRIDE |
AnnounceDate | 2020-05-20 |
AnnouncementXML | Submission_2020-05-20_05:20:56.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD015656 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Lindsey Hayes |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-10-01 05:17:38 | ID requested | |
⏵ 1 | 2020-05-20 05:20:57 | announced | |
Publication List
Hayes LR, Duan L, Bowen K, Kalab P, Rothstein JD, arginine-rich dipeptide repeat proteins disrupt karyopherin-mediated nuclear import. Elife, 9():(2020) [pubmed] |
Keyword List
submitter keyword: C9orf72, amyotrophic lateral sclerosis, importin beta, nuclear transport |
Contact List
Lindsey Hayes |
contact affiliation | Johns Hopkins |
contact email | lhayes@jhmi.edu |
lab head | |
Lindsey Hayes |
contact affiliation | Johns Hopkins University |
contact email | lhayes@jhmi.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD015656
- Label: PRIDE project
- Name: C9orf72 arginine-rich dipeptide repeat proteins disrupt importin beta-mediated nuclear import