title: Ataxin-10, the spinocerebellar ataxia type 10 neurodegenerative disorder protein, is essential for survival of cerebellar neurons.
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.
authors.affiliation: Institute of Physiology, Vesalgasse 1, University of Basel, 4051 Basel, Switzerland. p.maerz@unibas.ch
authors.forename: Pia
authors.initials: P
authors.lastname: März
authors.forename: Alphonse
authors.initials: A
authors.lastname: Probst
authors.forename: Sigrid
authors.initials: S
authors.lastname: Lang
authors.forename: Martine
authors.initials: M
authors.lastname: Schwager
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Uwe
authors.initials: U
authors.lastname: Otten
authors.forename: Suat
authors.initials: S
authors.lastname: Ozbek
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D000067736:Ataxin-10; D001483:Base Sequence; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D012091:Repetitive Sequences, Nucleic Acid; D020754:Spinocerebellar Ataxias / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D013132:Spinocerebellar Degenerations / Q000209:etiology / Q000235:genetics; D014018:Tissue Distribution
chemical_list: D000067736:Ataxin-10; C496258:Atxn10 protein, rat; D009419:Nerve Tissue Proteins