Mammalian LIN-7 PDZ proteins associate with beta-catenin at the cell-cell junctions of epithelia and neurons.
The heterotrimeric PDZ complex containing LIN-2, LIN-7 and LIN-10 is known to be involved in the organization of epithelial and neuronal junctions in Caenorhabditis elegans and mammals. We report here that mammalian LIN-7 PDZ proteins form a complex with cadherin and beta-catenin in epithelia and neurons. The association of LIN-7 with cadherin and beta-catenin is Ca(2+) dependent and is mediated by the direct binding of LIN-7 to the C-terminal PDZ target sequence of beta-catenin, as demonstrated by means of co-immunoprecipitation experiments and in vitro binding assays with the recombinant glutathione S-transferase:LIN-7A. The presence of beta-catenin at the junction is required in order to relocate LIN-7 from the cytosol to cadherin-mediated adhesions, thus indicating that LIN-7 junctional recruitment is beta-catenin dependent and that one functional role of the binding is to localize LIN-7. Moreover, when LIN-7 is present at the beta-catenin-containing junctions, it determines the accumulation of binding partners, thus suggesting the mechanism by which beta-catenin mediates the organization of the junctional domain.
CNR Cellular and Molecular Pharmacology Center, Department of Pharmacology, University of Milan, Via Vanvitelli 32, Italy. CarlaP@Farma.csfic.mi.cnr.it
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Perego
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Vanoni
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Massari
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Longhi
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Pietrini
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000302:isolation & purification; D002451:Cell Compartmentation; D002478:Cells, Cultured; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000302:isolation & purification*; D004285:Dogs; D004847:Epithelial Cells / Q000648:ultrastructure*; D006624:Hippocampus / Q000166:cytology; D007365:Intercellular Junctions / Q000648:ultrastructure*; D008565:Membrane Proteins / Q000302:isolation & purification*; D009474:Neurons / Q000648:ultrastructure*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013569:Synapses; D015534:Trans-Activators; D051176:beta Catenin
D015820:Cadherins; D003598:Cytoskeletal Proteins; C119588:LIN-7 protein, mammalian; D008565:Membrane Proteins; D015534:Trans-Activators; D051176:beta Catenin