HUNTINGTIN-ASSOCIATED PROTEIN (HAP1) - DISCRETE NEURONAL LOCALIZATIONS IN THE BRAIN RESEMBLE THOSE OF NEURONAL NITRIC-OXIDE SYNTHASE

Huntington disease stems from a mutation of the protein huntingtin and is characterized by selective loss of discrete neuronal populations i n the brain. Despite a massive loss of neurons in the corpus striatum, NO-generating neurons are intact. We recently identified a brain-spec ific protein that associates with huntingtin and is designated hunting tin-associated protein (HAP1). We now describe selective neuronal loca lizations of HAP1. In situ hybridization studies reveal a resemblance of HAP1 and neuronal nitric oxide synthase (nNOS) mRNA localizations w ith dramatic enrichment of both in the pedunculopontine nuclei, the ac cessory olfactory bulb, and the supraoptic nucleus of the hypothalamus . Both nNOS and HAP1 are enriched in subcellular fractions containing synaptic vesicles. Immunocytochemical studies indicate colocalizations of HAP1 and nNOS in some neurons. The possible relationship of HAP1 a nd nNOS in the brain is reminiscent of the relationship of dystrophin and nNOS in skeletal muscle and suggests a role of NO in Huntington di sease, analogous to its postulated role in Duchenne muscular dystrophy .