Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7

Spinocerebellar ataxia type 7 (SCA7) belongs to a group of neurological dis orders caused by a CAG repeat expansion in the coding region of the. associ ated gene. To gain insight into the pathogenesis of SCA7 and possible funct ions of ataxin-7, we examined the subcellular localization of ataxin-7 in t ransfected COS-1 cells using SCA7 cDNA clones with different CAG repeat tra ct lengths, In addition to a diffuse distribution throughout the nucleus, a taxin-7 associated with the nuclear matrix and the nucleolus. The location of the putative SCA7 nuclear localization sequence (NLS) was confirmed by f using an ataxin-7 fragment with the normally cytoplasmic protein chicken mu scle pyruvate kinase, Mutation of this NLS prevented protein from entering the nucleus. Thus, expanded ataxin-7 may carry out its pathogenic effects i n the nucleus by altering a matrix-associated nuclear structure and/or by d isrupting nucleolar function.