Abstract
Huntington disease (HD) is associated with the expansion of a polyglutamine tract, greater than 35 repeats, in the HD gene product, huntingtin. Here we describe a novel huntingtin interacting protein, HIP1, which co-localizes with huntingtin and shares sequence homology and biochemical characteristics with Sla2p, a protein essential for function of the cytoskeleton in Saccharomyces cerevisiae. The huntingtin-HIP1 interaction is restricted to the brain and is inversely correlated to the polyglutamine length in huntingtin. This provides the first molecular link between huntingtin and the neuronal cytoskeleton and suggests that, in HD, loss of normal huntingtin-HIP1 interaction may contribute to a defect in membrane-cytoskeletal integrity in the brain.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Blotting, Western
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Brain / cytology
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Brain / physiology*
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Caenorhabditis elegans / chemistry
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Caenorhabditis elegans / genetics
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Central Nervous System / metabolism
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Chromosome Mapping
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Chromosomes, Human, Pair 7
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Cloning, Molecular
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Cytoskeletal Proteins
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism
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Female
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Fungal Proteins / genetics*
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Helminth Proteins / genetics
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Humans
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Huntingtin Protein
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / immunology
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Nerve Tissue Proteins / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology
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Nuclear Proteins / metabolism*
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Peptides / chemistry
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Peptides / metabolism
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Precipitin Tests
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Rabbits
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae Proteins*
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Sequence Homology, Amino Acid
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Structure-Activity Relationship
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Subcellular Fractions
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Tissue Distribution
Substances
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Carrier Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Fungal Proteins
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HIP1 protein, human
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HTT protein, human
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Helminth Proteins
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Hip1 protein, mouse
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Htt protein, mouse
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Huntingtin Protein
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Nerve Tissue Proteins
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Nuclear Proteins
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Peptides
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Recombinant Fusion Proteins
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SLA2 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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polyglutamine
Associated data
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GENBANK/U79734
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GENBANK/Z22811