Ataxin-7 can export from the nucleus via a conserved exportin-dependent signal

doi:10.1074/jbc.M506751200

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Papers In Press, published online ahead of print November 28, 2005
J. Biol. Chem, 10.1074/jbc.M506751200
Submitted on June 21, 2005
Revised on October 25, 2005
Accepted on November 28, 2005

Ataxin-7 can export from the nucleus via a conserved exportin-dependent signal

Jillian Taylor, Sara K. Grote, Jianrun Xia, Mark Vandelft, Joanna Graczyk, Lisa M. Ellerby, Albert R. LaSpada, and Ray Truant

Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5

Corresponding Author: truantr{at}mcmaster.ca

Spinocerebellar ataxia type 7 (SCA7) is a progressive neurodegenerative disorder caused by a CAG DNA triplet repeat expansion leading to an expanded polyglutamine tract in the ataxin-7 protein. While the precise function of ataxin-7 is unknown, ataxin-7 appears to be a transcription factor, and component of the STAGA transcription co-activator complex. Here, using live cell imaging and inverted Fluorescence Recovery After Photobleaching with eGFP-ataxin-7, we demonstrate that ataxin-7 has the ability to export from the nucleus via the CRM-1/exportin pathway and that ataxin-7 contains a classic leucine-type nuclear export signal (NES). We have precisely defined the location of this NES in ataxin-7, and found it to be fully conserved in all vertebrate species. Polyglutamine expansion was seen to reduce the nuclear export rate of mutant ataxin-7 relative to wild-type ataxin-7. Subtle point-mutation of the NES in polyglutamine expanded ataxin-7 increased toxicity in primary cerebellar neurons in a polyglutamine length-dependent manner in the context of full-length ataxin-7. Our results add ataxin-7 to a growing list of polyglutamine disease proteins that are capable of nuclear shuttling, and we define an activity of ataxin-7 in the STAGA complex of trafficking between the nucleus and cytoplasm.

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