HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Blotting, Western, Brain, Caenorhabditis elegans, Carrier Proteins, Central Nervous System, Chromosome Mapping, Chromosomes, Human, Pair 7, Cloning, Molecular, Cytoskeletal Proteins, DNA-Binding Proteins, Female, Fungal Proteins, Helminth Proteins, Humans, Male, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Nerve Tissue Proteins, Nuclear Proteins, Peptides, Precipitin Tests, Rabbits, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Structure-Activity Relationship, Subcellular Fractions, Tissue Distribution
Amino Acid Sequence, Animals, Blotting, Western, Brain, Caenorhabditis elegans, Carrier Proteins, Central Nervous System, Chromosome Mapping, Chromosomes, Human, Pair 7, Cloning, Molecular, Cytoskeletal Proteins, DNA-Binding Proteins, Female, Fungal Proteins, Helminth Proteins, Humans, Male, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Nerve Tissue Proteins, Nuclear Proteins, Peptides, Precipitin Tests, Rabbits, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Structure-Activity Relationship, Subcellular Fractions, Tissue Distribution
Nat. Genet.
Date: May. 01, 1997
PubMed ID: 9140394
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