Abstract
Aggregation of conformation-abnormal peptides probably plays a key role in the pathogenesis of many neurodegenerative diseases. DSCR1 Down syndrome (DS) critical region 1, was identified from a chromosomal region (21q22.1-q22.2) for the clinical manifestations of DS when an extra-copy is present. We report that expression of DSCR1 in several cell types, including primary neurons, causes microtubule-dependent aggresome-like inclusion body formation. Disease-associated huntingtin (Q148) and ataxin-3 (Q84) co-localize with DSCR1 aggregates. Neurons bearing DSCR1 aggregates show reduced synaptophysin staining in processes. DSCR1 residues 31-90 constitute an aggregation-prone domain that is predicted to form a hydrophobic patch on the protein surface when residues 1-30 are removed. This study identifies a novel function of DSCR1 that may underlie DS neuropathology.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / pathology
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Animals
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Ataxin-3
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Cells, Cultured
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Chromosomes, Human, Pair 21 / genetics
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DNA-Binding Proteins
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Down Syndrome / genetics*
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Down Syndrome / pathology
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Gene Transfer Techniques
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Genes, Reporter
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Green Fluorescent Proteins
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Humans
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Huntingtin Protein
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Inclusion Bodies / metabolism*
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Inclusion Bodies / pathology
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins / genetics
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Macromolecular Substances
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Models, Molecular
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Muscle Proteins / genetics*
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Muscle Proteins / metabolism*
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Nerve Tissue Proteins / metabolism
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Neurons / metabolism*
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Neurons / pathology
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Nuclear Proteins / metabolism
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Protein Structure, Tertiary / genetics
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Protein Structure, Tertiary / physiology
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Rats
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Repressor Proteins
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Synapses / pathology*
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Synaptophysin / metabolism
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Ubiquitin / metabolism
Substances
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DNA-Binding Proteins
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HTT protein, human
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Htt protein, rat
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Huntingtin Protein
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins
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Macromolecular Substances
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Muscle Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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RCAN1 protein, human
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Repressor Proteins
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Synaptophysin
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Ubiquitin
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Green Fluorescent Proteins
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ATXN3 protein, human
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Ataxin-3
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Atxn3 protein, rat