Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD‐95

• Published in: Journal of neurochemistry 2004-08, Vol.90 (3), p.659-665
• Main Authors: Soltau, Michaela, Berhörster, Kerstin, Kindler, Stefan, Buck, Fritz, Richter, Dietmar, Kreienkamp, Hans‐Jürgen
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Biological and medical sciences; Brain Chemistry; Cell Line; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell physiology; Chromatography, Affinity; Disks Large Homolog 4 Protein; Fundamental and applied biological sciences. Psychology; Green Fluorescent Proteins; Guanylate Kinases; G‐protein; Humans; Intracellular Signaling Peptides and Proteins; Luminescent Proteins - genetics; Membrane Proteins; Mice; Miscellaneous; Molecular and cellular biology; Molecular Sequence Data; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons - metabolism; Neuropeptides - chemistry; Neuropeptides - metabolism; Nuclear Proteins; PDZ domain; Peptide Fragments - chemistry; Peptide Fragments - metabolism; ProSAP; Protein Binding - physiology; Protein Structure, Tertiary - genetics; Protein Structure, Tertiary - physiology; Rats; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; SSTRIP; Synapses - metabolism; Transcription Factors
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2004.02523.x

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).