Researchers at Johns Hopkins have discovered that a protein called rhes binds to the HD protein and causes toxicity
Researchers at Johns Hopkins have discovered that a protein called rhes binds to the HD protein and causes toxicity. Rhes is a protein found mostly in the striatum where brain damage is most extensive in Huntington’s Disease. It plays an important role in dopamine signaling in the medium spiny neurons; these are the neurons most affected by the disease.
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.