Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat which codes for glutamine in the protein ataxin-1. We have investigated the effect of this expansion on ataxin-1 by immunoblot analysis. The wild-type protein is detected in both normal and affected individuals; however, a mutant protein which varies in its migration properties according to the size of the CAG repeat is detected in cultured cells and tissues from SCA1 individuals. The protein has a nuclear localization in all normal and SCA1 brain regions examined but a cytoplasmic localization of ataxin-1 was also observed in cerebellar Purkinje cells. Our data show that in SCA1, the expanded alleles are faithfully translated into proteins of apparently normal stability and distribution.
Servadio
A
A
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Koshy
B
B
Armstrong
D
D
Antalffy
B
B
Orr
H T
HT
Zoghbi
H Y
HY
D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D001921:Brain / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D011689:Purkinje Cells / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012091:Repetitive Sequences, Nucleic Acid; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000378:metabolism
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; C000593751:Atxn1 protein, rat; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D005973:Glutamine