A huntingtin-associated protein enriched in brain with implications for pathology

HUNTINGTON’s disease (HD) is an autosomal dominant neuro-degenerative disorder caused by an expanding polyglutamine repeat in the IT 15 or huntingtin gene¹. Although this gene is widely expressed^2–9and is required for normal development^10–12, the pathology of HD is restricted to the brain, for reasons that remain poorly understood. The huntingtin gene product is expressed at similar levels in patients and controls, and the genetics of the disorder^13,14suggest that the expansion of the polyglutamine repeat induces a toxic gain of function, perhaps through interactions with other cellular proteins^15–18. Here we report the identification of a protein (huntingtin-associated protein (HAP)-l) that binds to huntingtin. This binding is enhanced by an expanded polyglutamine repeat, the length of which is also known to correlate with the age of disease onset^19–21. The HAP-1 protein is enriched in the brain, suggesting a possible basis for the selective brain pathology of HD.