Abstract
The insulin receptor substrate of 53 kDa (IRSp53) is a target of the small GTPase cdc42 which is strongly enriched in the postsynaptic density of excitatory synapses. IRSp53 interacts with the postsynaptic shank1 scaffolding molecule in a cdc42 regulated manner. The functional significance of the cdc42/IRSp53 pathway in postsynaptic sites is however, unclear. Here we identify PSD-95 as a second synaptic interaction partner of IRSp53. Interaction is mediated by a C-terminal PDZ binding motif in IRSp53 and the second PDZ domain of PSD-95. In HEK cells, overexpressed IRSp53 induces filopodia and targets PSD-95 into these processes. Immunoprecipitation and immunocytochemistry experiments demonstrate that the interaction occurs at postsynaptic sites in the brain. By virtue of its PDZ-binding and SH3 domains, IRSp53 is capable of inducing the formation of a triple complex (shank1/IRSp53/PSD-95).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing
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Amino Acid Sequence
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Animals
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Brain Chemistry
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Cell Line
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Cell Membrane / chemistry
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Cell Membrane / metabolism
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Chromatography, Affinity
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Disks Large Homolog 4 Protein
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Green Fluorescent Proteins
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Guanylate Kinases
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Humans
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins / genetics
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Membrane Proteins
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Mice
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism
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Neuropeptides / chemistry
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Neuropeptides / metabolism
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Nuclear Proteins*
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Protein Binding / physiology
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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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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Synapses / metabolism*
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Transcription Factors*
Substances
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BAIAP2 protein, human
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DLG3 protein, human
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Disks Large Homolog 4 Protein
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Dlg3 protein, rat
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Dlg4 protein, mouse
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Dlg4 protein, rat
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Neuropeptides
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Nuclear Proteins
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Peptide Fragments
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Recombinant Fusion Proteins
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Transcription Factors
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postsynaptic density proteins
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Green Fluorescent Proteins
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Dlgh3 protein, mouse
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Guanylate Kinases