Ataxin-10, the Spinocerebellar Ataxia Type 10 Neurodegenerative Disorder Protein, Is Essential for Survival of Cerebellar Neurons

• Published in: The Journal of biological chemistry 2004-08, Vol.279 (34), p.35542-35550
• Main Authors: März, Pia, Probst, Alphonse, Lang, Sigrid, Schwager, Martine, Rose-John, Stefan, Otten, Uwe, Ozbek, Suat
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Apoptosis - genetics; Ataxin-10; Base Sequence; Cell Survival - genetics; Cells, Cultured; Cerebellum - metabolism; Cerebellum - pathology; Down-Regulation; Humans; Mice; Molecular Sequence Data; Nerve Tissue Proteins - genetics; Rats; Rats, Wistar; Repetitive Sequences, Nucleic Acid; Spinocerebellar Ataxias - etiology; Spinocerebellar Ataxias - genetics; Spinocerebellar Ataxias - pathology; Spinocerebellar Degenerations - etiology; Spinocerebellar Degenerations - genetics; Tissue Distribution
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M405865200

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 ∼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.