title: The neuronal proteins CIPP, Cypin and IRSp53 form a tripartite complex mediated by PDZ and SH3 domains.
abstract: Here we report the dissection of a tripartite complex formed by CIPP (channel-interacting PDZ protein), IRSp53 (insulin receptor tyrosine kinase substrate protein) and Cypin (cytosolic PSD-95 interactor) in cultured cells. The three proteins are expressed in similar neuronal districts, where CIPP binds to different membrane channels and receptors, IRSp53 regulates the morphogenesis of actin-rich dendritic spines, and Cypin promotes dendrite branching and patterning by binding to tubulin heterodimers. We observed that the interaction among the three proteins is mediated by small binding domains: CIPP works as a bridge, linking the carboxy-termini of IRSp53 and Cypin with its PDZ domains; IRSp53 connects Cypin, through an unusual SH3-mediated association, which can be impaired by substituting two crucial positively charged residues of Cypin. The observation that the three engineered proteins co-localize in the cytoplasm, and at the tip of induced neurites in neuronal cells, raises the interesting possibility that they work together in the formation of neuronal protrusions.
authors: Cell and Developmental Biology Laboratory, Department of Biology, University of Pisa, I-56127 Pisa, Italy. mbarilari@biologia.unipi.it
authors: Manuela
authors: M
authors: Barilari
authors: Luciana
authors: L
authors: Dente
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D054731:PDZ Domains; D021381:Protein Transport; D018909:src Homology Domains
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins