Journal
CELL REPORTS
Volume 2, Issue 4, Pages 799-806Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2012.08.025
Keywords
-
Categories
Funding
- National Institutes of Health [GM043375, DP1OD003930]
- Toyobo Biotechnology Foundation
- ALS Therapy Alliance
- ALS Association
- Medical Research Council [G0900688, MC_G1000733, G0500289B, G0500289] Funding Source: researchfish
- MRC [G0500289, G0900688, MC_G1000733] Funding Source: UKRI
Ask authors/readers for more resources
Mutations in the RNA binding protein FUS cause amyotrophic lateral sclerosis (ALS), a fatal adult motor neuron disease. Decreased expression of SMN causes the fatal childhood motor neuron disorder spinal muscular atrophy (SMA). The SMN complex localizes in both the cytoplasm and nuclear Gems, and loss of Gems is a cellular hallmark of fibroblasts in patients with SMA. Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN. Functionally, we show that FUS is required for Gem formation in HeLa cells, and expression of FUS containing a severe ALS-causing mutation (R495X) also results in Gem loss. Strikingly, a reduction in Gems is observed in ALS patient fibroblasts expressing either mutant FUS or TDP-43, another ALS-causing protein that interacts with FUS. The physical and functional interactions among SMN, FUS, TDP-43, and Gems indicate that ALS and SMA share a biochemical pathway, providing strong support for the view that these motor neuron diseases are related.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available