title: Dynein binds to beta-catenin and may tether microtubules at adherens junctions.
abstract: Interactions between microtubule and actin networks are thought to be crucial for mechanical and signalling events at the cell cortex. Cytoplasmic dynein has been proposed to mediate many of these interactions. Here, we report that dynein is localized to the cortex at adherens junctions in cultured epithelial cells and that this localization is sensitive to drugs that disrupt the actin cytoskeleton. Dynein is recruited to developing contacts between cells, where it localizes with the junctional proteins beta-catenin and E-cadherin. Microtubules project towards these early contacts and we hypothesize that dynein captures and tethers microtubules at these sites. Dynein immunoprecipitates with beta-catenin, and biochemical analysis shows that dynein binds directly to beta-catenin. Overexpression of beta-catenin disrupts the cellular localization of dynein and also dramatically perturbs the organization of the cellular microtubule array. In cells overexpressing beta-catenin, the centrosome becomes disorganized and microtubules no longer appear to be anchored at the cortex. These results identify a novel role for cytoplasmic dynein in capturing and tethering microtubules at adherens junctions, thus mediating cross-talk between actin and microtubule networks at the cell cortex.
authors.affiliation: Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Ligon
authors.forename: S
authors.initials: S
authors.lastname: Karki
authors.forename: M
authors.initials: M
authors.lastname: Tokito
authors.forename: E L
authors.initials: EL
authors.lastname: Holzbaur
mesh_terms: D022005:Adherens Junctions / Q000737:chemistry / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D011233:Precipitin Tests; D011485:Protein Binding; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003598:Cytoskeletal Proteins; D013844:Thiazoles; D053778:Thiazolidines; D015534:Trans-Activators; D051176:beta Catenin; D004398:Dyneins; C037068:latrunculin B; D015739:Nocodazole