Report

Rhes, a Striatal Specific Protein, Mediates Mutant-Huntingtin Cytotoxicity

Science  05 Jun 2009:
Vol. 324, Issue 5932, pp. 1327-1330
DOI: 10.1126/science.1172871

You are currently viewing the abstract.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Abstract

Huntington’s disease (HD) is caused by a polyglutamine repeat in the protein huntingtin (Htt) with mutant Htt (mHtt) expressed throughout the body and similarly in all brain regions. Yet, HD neuropathology is largely restricted to the corpus striatum. We report that the small guanine nucleotide–binding protein Rhes, which is localized very selectively to the striatum, binds physiologically to mHtt. Using cultured cells, we found Rhes induces sumoylation of mHtt, which leads to cytotoxicity. Thus, Rhes-mHtt interactions can account for the localized neuropathology of HD.

View Full Text

Cited By...