title: Family-wide investigation of PDZ domain-mediated protein-protein interactions implicates β-catenin in maintaining the integrity of tight junctions.
abstract: β-catenin is a multifunctional protein that plays a critical role in cell-cell contacts and signal transduction. β-catenin has previously been shown to interact with PDZ-domain-containing proteins through its C terminus. Using protein microarrays comprising 206 mouse PDZ domains, we identified 26 PDZ-domain-mediated interactions with β-catenin and confirmed them biochemically and in cellular lysates. Many of the previously unreported interactions involved proteins with annotated roles in tight junctions. We found that four tight-junction-associated PDZ proteins-Scrib, Magi-1, Pard3, and ZO-3-colocalize with β-catenin at the plasma membrane. Disrupting these interactions by RNA interference, overexpression of PDZ domains, or overexpression of the β-catenin C terminus altered localization of the full-length proteins, weakened tight junctions, and decreased cellular adhesion. These results suggest that β-catenin serves as a scaffold to establish the location and function of tight-junction-associated proteins.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Taranjit S
authors.initials: TS
authors.lastname: Gujral
authors.forename: Ethan S
authors.initials: ES
authors.lastname: Karp
authors.forename: Marina
authors.initials: M
authors.lastname: Chan
authors.forename: Bryan H
authors.initials: BH
authors.lastname: Chang
authors.forename: Gavin
authors.initials: G
authors.lastname: MacBeath
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D005454:Fluorescence Polarization; D051528:Guanylate Kinases; D057809:HEK293 Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D054731:PDZ Domains; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D018797:Cell Cycle Proteins; C111442:MPDZ protein, human; D008565:Membrane Proteins; C509689:PARD3 protein, human; D034741:RNA, Small Interfering; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D051528:Guanylate Kinases; C113338:MAGI1 protein, human