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 journalArticle

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

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Nitric Oxide Synthase Type I
Brain
Huntington Disease
Neurons
Corpus Striatum
Supraoptic Nucleus
Dystrophin
Subcellular Fractions
Duchenne Muscular Dystrophy
Synaptic Vesicles
Olfactory Bulb
In Situ Hybridization
Skeletal Muscle
Huntingtin Protein
Messenger RNA
Mutation
Population
Proteins

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "Huntingtin-associated protein (HAP1): Discrete neuronal localizations in the brain resemble those of neuronal nitric oxide synthase",
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.",
keywords = "dystrophin, excitotoxicity, glutamate, Huntington disease, muscular dystrophy",
author = "Li, {Xiao Jiang} and Sharp, {Alan H.} and Li, {Shi Hua} and Dawson, {Ted M} and Snyder, {Solomon H} and Ross, {Christopher A}",
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T2 - Discrete neuronal localizations in the brain resemble those of neuronal nitric oxide synthase

AU - Li, Xiao Jiang

AU - Sharp, Alan H.

AU - Li, Shi Hua

AU - Dawson, Ted M

AU - Snyder, Solomon H

AU - Ross, Christopher A

PY - 1996/5/14

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N2 - 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.

AB - 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.

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KW - muscular dystrophy

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