Open Close
Reference
Citation
Bogaert, E., Boeynaems, S., Kato, M., Guo, L., Caulfield, T.R., Steyaert, J., Scheveneels, W., Wilmans, N., Haeck, W., Hersmus, N., Schymkowitz, J., Rousseau, F., Shorter, J., Callaerts, P., Robberecht, W., Van Damme, P., Van Den Bosch, L. (2018). Molecular Dissection of FUS Points at Synergistic Effect of Low-Complexity Domains in Toxicity.  Cell Rep. 24(3): 529--537.e4.
FlyBase ID
FBrf0239492
Publication Type
Research paper
Abstract

RNA-binding protein aggregation is a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). To gain better insight into the molecular interactions underlying this process, we investigated FUS, which is mutated and aggregated in both ALS and FTLD. We generated a Drosophila model of FUS toxicity and identified a previously unrecognized synergistic effect between the N-terminal prion-like domain and the C-terminal arginine-rich domain to mediate toxicity. Although the prion-like domain is generally considered to mediate aggregation of FUS, we find that arginine residues in the C-terminal low-complexity domain are also required for maturation of FUS in cellular stress granules. These data highlight an important role for arginine-rich domains in the pathology of RNA-binding proteins.

PubMed ID
PubMed Central ID
PMC6077250 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Rep.
    Title
    Cell reports
    ISBN/ISSN
    2211-1247
    Data From Reference
    Alleles (31)
    Genes (3)
    Human Disease Models (1)
    Natural transposons (2)
    Insertions (22)
    Experimental Tools (1)
    Transgenic Constructs (29)