Polyglutamine and polyalanine expansions in ataxin7 result in different types of aggregation and levels of toxicity.
Molecular and Cellular Neuroscience. 2006-03-01; 31(3): 438-445
DOI: 10.1016/j.mcn.2005.10.013
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1. Mol Cell Neurosci. 2006 Mar;31(3):438-45. Epub 2005 Dec 1.
Polyglutamine and polyalanine expansions in ataxin7 result in different types of
aggregation and levels of toxicity.
Latouche M(1), Fragner P, Martin E, El Hachimi KH, Zander C, Sittler A, Ruberg M,
Brice A, Stevanin G.
Author information:
(1)INSERM U679 (former U289), Neurologie et Thérapeutique Expérimentale, Groupe
Hospitalier Pitié-Salpêtrière, Paris, France.
Spinocerebellar ataxia type 7 (SCA7) is caused by expansion of a (CAG)n repeat in
the ataxin7 gene, resulting in an abnormally long polyglutamine polyQ tract in
the translated protein that aggregates in the form of neuronal intranuclear
inclusions. Polyalanine (polyA) stretches, implicated in several genetic
disorders, also appear to aggregate. To investigate the role of the aggregates in
the pathologies, we compared the effects of ataxin7 containing a polyA (ataxin7 –
90A) or polyQ (ataxin7 – 100Q) expansion in HEK 293 cells and in primary cultures
of rat mesencephalon. Both proteins formed nuclear and perinuclear aggregates
that contained molecular chaperones and components of the ubiquitin-proteasome
system, suggesting that they were abnormally folded. Ataxin-90A aggregates
differed morphologically from ataxin7 – 100Q aggregates, consisted of small and
amorphous rather than fibrillar inclusions and were more toxic to mesencephalic
neurons, suggesting that toxicity was determined by the type of aggregate rather
than the cellular misfolding response.
DOI: 10.1016/j.mcn.2005.10.013
PMID: 16325416 [Indexed for MEDLINE]