E-resources
-
Farg, Manal A; Soo, Kai Y; Warraich, Sadaf T; Sundaramoorthy, Vinod; Blair, Ian P; Atkin, Julie D
Human molecular genetics, 02/2013, Volume: 22, Issue: 4Journal Article
Fused in sarcoma (FUS) is mutated in both sporadic amyotrophic lateral sclerosis (ALS) and familial ALS patients. The mechanisms underlying neurodegeneration are not fully understood, but FUS redistributes from the nucleus to the cytoplasm in affected motor neurons, where it triggers endoplasmic reticulum (ER) stress. Ataxin-2 is a polyglutamine protein which normally contains 22 repeats, but expanded repeats (>34) are found in Spinocerebellar Ataxia type 2. Recently ataxin-2 with intermediate length repeats (27-33) was found to increase the risk of ALS. Here we show that ataxin-2 with an ALS-linked intermediate length repeat (Q31) is a potent modifier of FUS pathology in cellular disease models. Translocation of FUS to the cytoplasm and ER stress were significantly enhanced by co-expression of mutant FUS with ataxin-2 Q31. Ataxin-2 also co-localized with FUS in sporadic and FUS-linked familial ALS patient motor neurons, co-precipitated with FUS in ALS spinal cord lysates, and co-localized with FUS in the ER-Golgi compartments in neuronal cell lines. Fragmentation of the Golgi apparatus is linked to neurodegeneration in ALS and here we show that Golgi fragmentation is induced in cells expressing mutant FUS. Moreover, Golgi fragmentation was enhanced, and the early stages of apoptosis were triggered, when ataxin-2 Q31 was co-expressed with mutant FUS. These findings describe new cellular mechanisms linking ALS with ataxin-2 intermediate length polyQ expansions and provide further evidence linking disruption to ER-Golgi compartments and FUS pathology in ALS.
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.