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PXD015656

PXD015656 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleC9orf72 arginine-rich dipeptide repeat proteins disrupt importin beta-mediated nuclear import
DescriptionDisruption 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.
HostingRepositoryPRIDE
AnnounceDate2020-05-20
AnnouncementXMLSubmission_2020-05-20_05:20:56.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD015656
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterLindsey Hayes
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-10-01 05:17:38ID requested
12020-05-20 05:20:57announced
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 affiliationJohns Hopkins
contact emaillhayes@jhmi.edu
lab head
Lindsey Hayes
contact affiliationJohns Hopkins University
contact emaillhayes@jhmi.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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