GSBS Student Publications

Title

Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules

Student Author(s)

Hae Kyung Ko

GSBS Program

Cell Biology

UMMS Affiliation

Department of Neurology

Date

11-1-2010

Document Type

Article

Disciplines

Molecular Genetics | Nervous System Diseases | Neurology | Neuroscience and Neurobiology

Abstract

Mutations in the RNA-binding protein FUS (fused in sarcoma) are linked to amyotrophic lateral sclerosis (ALS), but the mechanism by which these mutants cause motor neuron degeneration is not known. We report a novel ALS truncation mutant (R495X) that leads to a relatively severe ALS clinical phenotype compared with FUS missense mutations. Expression of R495X FUS, which abrogates a putative nuclear localization signal at the C-terminus of FUS, in HEK-293 cells and in the zebrafish spinal cord caused a striking cytoplasmic accumulation of the protein to a greater extent than that observed for recessive (H517Q) and dominant (R521G) missense mutants. Furthermore, in response to oxidative stress or heat shock conditions in cultures and in vivo, the ALS-linked FUS mutants, but not wild-type FUS, assembled into perinuclear stress granules in proportion to their cytoplasmic expression levels. These findings demonstrate a potential link between FUS mutations and cellular pathways involved in stress responses that may be relevant to altered motor neuron homeostasis in ALS.

DOI of Published Version

10.1093/hmg/ddq335

Source

Hum Mol Genet. 2010 Nov 1;19(21):4160-75. doi: 10.1093/hmg/ddq335. Epub 2010 Aug 10. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Human molecular genetics

PubMed ID

20699327

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