Abstract
Synaptogenesis and synaptic plasticity depend crucially on the dynamic and locally specific regulation of the actin cytoskeleton. We identified an important component for controlled actin assembly, abelson interacting protein-1 (Abi-1), as a binding partner for the postsynaptic density (PSD) protein ProSAP2/Shank3. During early neuronal development, Abi-1 is localized in neurites and growth cones; at later stages, the protein is enriched in dendritic spines and PSDs, as are components of a trimeric complex consisting of Abi-1, Eps8 and Sos-1. Abi-1 translocates upon NMDA application from PSDs to nuclei. Nuclear entry depends on abelson kinase activity. Abi-1 co-immunoprecipitates with the transcription factor complex of Myc/Max proteins and enhances E-box-regulated gene transcription. Downregulation of Abi-1 by small interfering RNA results in excessive dendrite branching, immature spine and synapse morphology and a reduction of synapses, whereas overexpression of Abi-1 has the opposite effect. Data show that Abi-1 can act as a specific synapto-nuclear messenger and is essentially involved in dendrite and synapse formation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Sequence
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Animals
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Blotting, Western
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Brain / drug effects
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Brain / metabolism
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Cells, Cultured
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Dendrites / drug effects
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Dendrites / metabolism*
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Dendrites / physiology
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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In Situ Hybridization
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Molecular Sequence Data
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N-Methylaspartate / pharmacology
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurons / drug effects
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Neurons / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Phosphorylation
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Proline / chemistry
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Proline / metabolism
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Protein Binding
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Rats
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Synapses / drug effects
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Synapses / metabolism*
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Synapses / physiology
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Two-Hybrid System Techniques
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Tyrosine / chemistry
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Tyrosine / metabolism
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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Cytoskeletal Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Recombinant Fusion Proteins
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Shank3 protein, rat
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postsynaptic density proteins
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Green Fluorescent Proteins
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Tyrosine
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N-Methylaspartate
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Proline