title: Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD-95.
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).
authors.affiliation: Institut für Zellbiochemie und klinische Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Soltau
authors.forename: Kerstin
authors.initials: K
authors.lastname: Berhörster
authors.forename: Stefan
authors.initials: S
authors.lastname: Kindler
authors.forename: Fritz
authors.initials: F
authors.lastname: Buck
authors.forename: Dietmar
authors.initials: D
authors.lastname: Richter
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Kreienkamp
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002846:Chromatography, Affinity; D000076122:Disks Large Homolog 4 Protein; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: C119539:BAIAP2 protein, human; C116869:DLG3 protein, human; D000076122:Disks Large Homolog 4 Protein; C101195:Dlg3 protein, rat; C501447:Dlg4 protein, mouse; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins; C491075:Dlgh3 protein, mouse; D051528:Guanylate Kinases