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ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import
Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than ME, Mackenzie IR et al.. The EMBO journal, 2010-07-06
Topic: Brain proteins, microglia and lab models
Plain-language summary
Mutations in fused in sarcoma (FUS) are a cause of familial amyotrophic lateral sclerosis (fALS). Patients carrying point mutations in the C-terminus of FUS show neuronal cytoplasmic FUS-positive inclusions, whereas in healthy controls, FUS is predominantly nuclear. Cytoplasmic FUS inclusions have also been identified in a subset of frontotemporal lobar degeneration (FTLD-FUS). We show that a non-classical PY nuclear localization signal (NLS) in the C-terminus of FUS is necessary for nuclear import. The majority of fALS-associated mutations occur within the NLS and impair nuclear import to a degree that correlates with the age of disease onset. This presents the first case of disease-causing mutations within a PY-NLS. Nuclear import of FUS is dependent on Transportin, and interference with this transport pathway leads to cytoplasmic redistribution and recruitment of FUS into stress granules. Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies.
What this study adds
Evidence grade: Low
This laboratory study found that many ALS-associated mutations in the FUS protein disrupt its normal transport into the nucleus, leading to clumps in the cytoplasm. It proposes that nuclear import defects and cellular stress are involved in FUS-related diseases, but this is mechanistic research and not a treatment.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Dormann, D., Rodde, R., Edbauer, D., Bentmann, E., Fischer, I., Hruscha, A., et al. (2010). ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. The EMBO journal. https://doi.org/10.1038/emboj.2010.143
Vancouver
Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, et al. ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. The EMBO journal. 2010. doi:10.1038/emboj.2010.143. PMID: 20606625.
BibTeX
@article{dormann2010-20606625,
author = {Dormann, D. and Rodde, R. and Edbauer, D. and Bentmann, E. and Fischer, I. and Hruscha, A. and Than, M. E. and Mackenzie, I. R. and others},
title = {{ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import}},
journal = {The EMBO journal},
year = {2010},
doi = {10.1038/emboj.2010.143},
pmid = {20606625},
url = {https://doi.org/10.1038/emboj.2010.143}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- The majority of fALS-associated mutations occur within the NLS and impair nuclear import to a degree that correlates with the age of disease onset.
- This presents the first case of disease-causing mutations within a PY-NLS.
- Nuclear import of FUS is dependent on Transportin, and interference with this transport pathway leads to cytoplasmic redistribution and recruitment of FUS into stress granules.
- Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases.
- We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies.
Why it matters
This laboratory study found that many ALS-associated mutations in the FUS protein disrupt its normal transport into the nucleus, leading to clumps in the cytoplasm. It proposes that nuclear import defects and cellular stress are involved in FUS-related diseases, but this is mechanistic research and not a treatment.
Study details
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The EMBO journal) |
| Journal's citation record | 4 / 4 | The EMBO Journal: journal h-index 563 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 834 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 46.3 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 5 / 6 | Cited 32.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 20 other studies in this library |
| Still being cited | 3 / 4 | Cited 105 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Christian Haass: h-index 139 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20606625) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
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