Huntingtin-associated protein (HAP1): Discrete neuronal localizations in the brain resemble those of neuronal nitric oxide synthase

Xiao Jiang Li, Alan H. Sharp, Shi Hua Li, Ted M. Dawson, Solomon H. Snyder, Christopher A. Ross

Research output: Contribution to journalArticlepeer-review

Abstract

Huntington disease stems from a mutation of the protein huntingtin and is characterized by selective loss of discrete neuronal populations in the brain. Despite a massive loss of neurons in the corpus striatum, NO- generating neurons are intact. We recently identified a brain-specific protein that associates with huntingtin and is designated huntingtin- associated protein (HAP1). We now describe selective neuronal localizations of HAP1. In situ hybridization studies reveal a resemblance of HAP1 and neuronal nitric oxide synthase (nNOS) mRNA localizations with dramatic enrichment of both in the pedunculopontine nuclei, the accessory 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 and nNOS in the brain is reminiscent of the relationship of dystrophin and nNOS in skeletal muscle and suggests a role of NO in Huntington disease, analogous to its postulated role in Duchenne muscular dystrophy.

Original languageEnglish (US)
Pages (from-to)4839-4844
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number10
DOIs
StatePublished - May 14 1996

Keywords

  • Huntington disease
  • dystrophin
  • excitotoxicity
  • glutamate
  • muscular dystrophy

ASJC Scopus subject areas

  • General

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