Ataxin-10, the spinocerebellar ataxia type 10 neurodegenerative disorder protein, is essential for survival of cerebellar neurons |
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Authors: | März Pia Probst Alphonse Lang Sigrid Schwager Martine Rose-John Stefan Otten Uwe Ozbek Suat |
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Institution: | Institute of Physiology, Vesalgasse 1, University of Basel, 4051 Basel, Switzerland. p.maerz@unibas.ch |
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Abstract: | Spinocerebellar ataxia (SCA) type 10, an autosomal dominant disease characterized by cerebellar ataxia, is caused by a novel pentanucleotide (ATTCT) repeat expansion in the SCA10 gene. Although clinical features of the disease are well characterized, nothing is known so far about the affected SCA10 gene product, ataxin-10 (Atx-10). We have cloned the rat SCA10 gene and expressed the corresponding protein in HEK293 cells. Atx-10 has an apparent molecular mass of approximately 55 kDa and belongs to the family of armadillo repeat proteins. In solution, it tends to form homotrimeric complexes, which associate via a tip-to-tip contact with the concave sides of the molecules facing each other. Atx-10 immunostaining of mouse and human brain sections revealed a predominantly cytoplasmic and perinuclear localization with a clear restriction to olivocerebellar regions. Knock down of SCA10 in primary neuronal cells by small interfering RNAs resulted in an increased apoptosis of cerebellar neurons, arguing for a loss-of-function phenotype in SCA10 patients. |
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