Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD-95.
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).
Mesh Terms:
Alternative Splicing, Amino Acid Sequence, Animals, Brain Chemistry, Cell Line, Cell Membrane, Chromatography, Affinity, Disks Large Homolog 4 Protein, Green Fluorescent Proteins, Guanylate Kinases, Humans, Intracellular Signaling Peptides and Proteins, Luminescent Proteins, Membrane Proteins, Mice, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Neuropeptides, Nuclear Proteins, Peptide Fragments, Protein Binding, Protein Structure, Tertiary, Rats, Recombinant Fusion Proteins, Synapses, Transcription Factors
Alternative Splicing, Amino Acid Sequence, Animals, Brain Chemistry, Cell Line, Cell Membrane, Chromatography, Affinity, Disks Large Homolog 4 Protein, Green Fluorescent Proteins, Guanylate Kinases, Humans, Intracellular Signaling Peptides and Proteins, Luminescent Proteins, Membrane Proteins, Mice, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Neuropeptides, Nuclear Proteins, Peptide Fragments, Protein Binding, Protein Structure, Tertiary, Rats, Recombinant Fusion Proteins, Synapses, Transcription Factors
J. Neurochem.
Date: Aug. 01, 2004
PubMed ID: 15255944
View in: Pubmed Google Scholar
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