title: GSK-3beta-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome.
abstract: Microtubule arrays direct intracellular organization and define cellular polarity. Here, we show a novel function of glycogen synthase kinase-3beta (GSK-3beta) in the organization of microtubule arrays through the interaction with Bicaudal-D (BICD). BICD is known to form a complex with dynein-dynactin and to function in the intracellular vesicle trafficking. Our data revealed that GSK-3beta is required for the binding of BICD to dynein but not to dynactin. Knockdown of GSK-3beta or BICD reduced centrosomally focused microtubules and induced the mislocalization of centrosomal proteins. The unfocused microtubules in GSK-3beta knockdown cells were rescued by the expression of the dynein intermediate chain-BICD fusion protein. Microtubule regrowth assays showed that GSK-3beta and BICD are required for the anchoring of microtubules to the centrosome. These results imply that GSK-3beta may function in transporting centrosomal proteins to the centrosome by stabilizing the BICD1 and dynein complex, resulting in the regulation of a focused microtubule organization.
authors.affiliation: Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fumoto
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D018385:Centrosome / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109571:BICD1 protein, human; D003598:Cytoskeletal Proteins; C512806:NIN protein, human; D009687:Nuclear Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D004398:Dyneins