Abstract
Huntington@s disease (HD) is an autosomal-dominant neurodegenerative disease caused by the expansion of polyglutamine repeats in the gene for huntingtin (. Htt). In HD, the corpus striatum selectively degenerates despite the uniform expression of mutant huntingtin (mHtt) throughout the brain and body. Striatal selectivity reflects the binding of the striatal-selective protein Rhes to mHtt to augment cytotoxicity, but molecular mechanisms underlying the toxicity have been elusive. Here, we report that the Golgi protein acyl-CoA binding domain containing 3 (ACBD3) mediates mHtt cytotoxicity via a Rhes/mHtt/ACBD3 complex. ACBD3 levels are markedly elevated in the striatum of HD patients, in a striatal cell line harboring polyglutamine repeats, and in the brains of HD mice. Moreover, ACBD3 deletion abolishes HD neurotoxicity, which is increased by ACBD3 overexpression. Enhanced levels of ACBD3 elicited by endoplasmic reticulum, mitochondrial, and Golgi stresses may account for HD-associated augmentation of ACBD3 and neurodegeneration
| Original language | English (US) |
|---|---|
| Pages (from-to) | 890-897 |
| Number of pages | 8 |
| Journal | Cell Reports |
| Volume | 4 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 12 2013 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
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Golgi protein ACBD3 mediates neurotoxicity associated with huntington's disease. / Sbodio, Juan; Paul, Bindu; Machamer, Carolyn E; Snyder, Solomon H.
In: Cell Reports, Vol. 4, No. 5, 12.05.2013, p. 890-897.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Golgi protein ACBD3 mediates neurotoxicity associated with huntington's disease
AU - Sbodio, Juan
AU - Paul, Bindu
AU - Machamer, Carolyn E
AU - Snyder, Solomon H
PY - 2013/5/12
Y1 - 2013/5/12
N2 - Huntington@s disease (HD) is an autosomal-dominant neurodegenerative disease caused by the expansion of polyglutamine repeats in the gene for huntingtin (. Htt). In HD, the corpus striatum selectively degenerates despite the uniform expression of mutant huntingtin (mHtt) throughout the brain and body. Striatal selectivity reflects the binding of the striatal-selective protein Rhes to mHtt to augment cytotoxicity, but molecular mechanisms underlying the toxicity have been elusive. Here, we report that the Golgi protein acyl-CoA binding domain containing 3 (ACBD3) mediates mHtt cytotoxicity via a Rhes/mHtt/ACBD3 complex. ACBD3 levels are markedly elevated in the striatum of HD patients, in a striatal cell line harboring polyglutamine repeats, and in the brains of HD mice. Moreover, ACBD3 deletion abolishes HD neurotoxicity, which is increased by ACBD3 overexpression. Enhanced levels of ACBD3 elicited by endoplasmic reticulum, mitochondrial, and Golgi stresses may account for HD-associated augmentation of ACBD3 and neurodegeneration
AB - Huntington@s disease (HD) is an autosomal-dominant neurodegenerative disease caused by the expansion of polyglutamine repeats in the gene for huntingtin (. Htt). In HD, the corpus striatum selectively degenerates despite the uniform expression of mutant huntingtin (mHtt) throughout the brain and body. Striatal selectivity reflects the binding of the striatal-selective protein Rhes to mHtt to augment cytotoxicity, but molecular mechanisms underlying the toxicity have been elusive. Here, we report that the Golgi protein acyl-CoA binding domain containing 3 (ACBD3) mediates mHtt cytotoxicity via a Rhes/mHtt/ACBD3 complex. ACBD3 levels are markedly elevated in the striatum of HD patients, in a striatal cell line harboring polyglutamine repeats, and in the brains of HD mice. Moreover, ACBD3 deletion abolishes HD neurotoxicity, which is increased by ACBD3 overexpression. Enhanced levels of ACBD3 elicited by endoplasmic reticulum, mitochondrial, and Golgi stresses may account for HD-associated augmentation of ACBD3 and neurodegeneration
UR - http://www.scopus.com/inward/record.url?scp=84884138290&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884138290&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2013.08.001
DO - 10.1016/j.celrep.2013.08.001
M3 - Article
C2 - 24012756
AN - SCOPUS:84884138290
VL - 4
SP - 890
EP - 897
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 5
ER -