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

Michael D. Kaytor, Lisa A. Duvick, Pamela J. Skinner, Michael D. Koob, Laura P.W. Ranum, Harry T. Orr

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Spinocerebellar ataxia type 7 (SCA7) belongs to a group of neurological disorders caused by a CAG repeat expansion in the coding region of the associated gene. To gain insight into the pathogenesis of SCA7 and possible functions of ataxin-7, we examined the subcellular localization of ataxin-7 in transfected COS-1 cells using SCA7 cDNA clones with different CAG repeat tract lengths. In addition to a diffuse distribution throughout the nucleus, ataxin-7 associated with the nuclear matrix and the nucleolus. The location of the putative SCA7 nuclear localization sequence (NLS) was confirmed by fusing an ataxin-7 fragment with the normally cytoplasmic protein chicken muscle pyruvate kinase. Mutation of this NLS prevented protein from entering the nucleus. Thus, expanded ataxin-7 may carry out its pathogenic effects in the nucleus by altering a matrix-associated nuclear structure and/or by disrupting nucleolar function.

Original languageEnglish (US)
Pages (from-to)1657-1664
Number of pages8
JournalHuman molecular genetics
Volume8
Issue number9
DOIs
StatePublished - Sep 17 1999

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