Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
DOI
PMC
 |
|
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Arginine methylation next to the PY-NLS modulates transportin binding and nuclear import of FUS.
EMBO J. 31, 4258-4275 (2012)
Fused in sarcoma (FUS) is a nuclear protein that carries a proline-tyrosine nuclear localization signal (PY-NLS) and is imported into the nucleus via Transportin (TRN). Defects in nuclear import of FUS have been implicated in neurodegeneration, since mutations in the PY-NLS of FUS cause amyotrophic lateral sclerosis (ALS). Moreover, FUS is deposited in the cytosol in a subset of frontotemporal lobar degeneration (FTLD) patients. Here, we show that arginine methylation modulates nuclear import of FUS via a novel TRN-binding epitope. Chemical or genetic inhibition of arginine methylation restores TRN-mediated nuclear import of ALS-associated FUS mutants. The unmethylated arginine-glycine-glycine domain preceding the PY-NLS interacts with TRN and arginine methylation in this domain reduces TRN binding. Inclusions in ALS-FUS patients contain methylated FUS, while inclusions in FTLD-FUS patients are not methylated. Together with recent findings that FUS co-aggregates with two related proteins of the FET family and TRN in FTLD-FUS but not in ALS-FUS, our study provides evidence that these two diseases may be initiated by distinct pathomechanisms and implicates alterations in arginine methylation in pathogenesis.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
amyotrophic lateral sclerosis (ALS); arginine methylation; frontotemporal lobar degeneration (FTLD); fused in sarcoma (FUS); Transportin (TRN)
ISSN (print) / ISBN
0261-4189
e-ISSN
1460-2075
Journal
EMBO Journal, The
Quellenangaben
Volume: 31,
Issue: 22,
Pages: 4258-4275
Publisher
Wiley
Publishing Place
Heidelberg, Germany
Reviewing status
Peer reviewed