PXD015656

PXD015656 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-01 05:17:38	ID requested
⏵ 1	2020-05-20 05:20:57	announced

Hayes LR, Duan L, Bowen K, Kalab P, Rothstein JD, arginine-rich dipeptide repeat proteins disrupt karyopherin-mediated nuclear import. Elife, 9():(2020) [pubmed]

submitter keyword: C9orf72, amyotrophic lateral sclerosis, importin beta, nuclear transport

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

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PRIDE project URI

• PRIDE
  1. PXD015656
     1. Label: PRIDE project
     2. Name: C9orf72 arginine-rich dipeptide repeat proteins disrupt importin beta-mediated nuclear import