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Aggregate formation and synaptic abnormality induced by DSCR1.

Hong Ma·Hui Xiong·Tong Liu·Lingyan Zhang·Adam Godzik·Zhuohua Zhang
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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.

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Alzheimer DiseaseAnimalsAtaxin-3Cells, CulturedChromosomes, Human, Pair 21DNA-Binding ProteinsDown SyndromeGene Transfer TechniquesGenes, ReporterGreen Fluorescent ProteinsHumansHuntingtin ProteinInclusion BodiesIntracellular Signaling Peptides and ProteinsLuminescent ProteinsMacromolecular SubstancesModels, MolecularMuscle ProteinsNerve Tissue ProteinsNeuronsNuclear ProteinsProtein Structure, TertiaryRatsRepressor ProteinsSynapsesSynaptophysinUbiquitinJournal ArticleResearch Support, Non-U.S. Gov't

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Hong Ma, Hui Xiong, Tong Liu, Lingyan Zhang, Adam Godzik, Zhuohua Zhang. 2004. Aggregate formation and synaptic abnormality induced by DSCR1.. https://doi.org/10.1046/j.1471-4159.2003.02294.x

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