The localization and interactions of huntingtin

Huntingtin was localized by using a series of antibodies that detected diff erent areas of the protein from the immediate N-terminus to the C-terminal region of the protein. The more C-terminal antibodies gave a cytoplasmic lo calization in neurons of the brain in controls and cases of Huntington's di sease (HD). The N-terminal antibody, however, gave a distinctive pattern of immunoreactivity in the HD brain,with marked staining of axon tracts and w hite matter and the detection of densely staining intranuclear inclusions. This implies some processing differences between mutated and normal hunting tin. We have also localized two interacting proteins, cystathionine beta-sy nthase and the nuclear receptor co-repressor (N-CoR), in brain. Cystathioni ne beta-synthase was not relocalized in HD brain, but the N-CoR was exclude d from neuronal nuclei in HD brain, and a further protein that exists in th e same repression complex, mSin3, was similarly excluded. We conclude that the co-repressor might have a part in HD pathology.