title: Kinesin-II recruits Armadillo and Dishevelled for Wingless signaling in Drosophila.
abstract: Wingless (Wg)/Wnt signaling is fundamental in metazoan development. Armadillo (Arm)/β-catenin and Dishevelled (Dsh) are key components of Wnt signal transduction. Recent studies suggest that intracellular trafficking of Wnt signaling components is important, but underlying mechanisms are not well known. Here, we show that Klp64D, the Drosophila homolog of Kif3A kinesin II subunit, is required for Wg signaling by regulating Arm during wing development. Mutations in klp64D or RNAi cause wing notching and loss of Wg target gene expression. The wing notching phenotype by Klp64D knockdown is suppressed by activated Arm but not by Dsh, suggesting that Klp64D is required for Arm function. Furthermore, klp64D and arm mutants show synergistic genetic interaction. Consistent with this genetic interaction, Klp64D directly binds to the Arm repeat domain of Arm and can recruit Dsh in the presence of Arm. Overexpression of Klp64D mutated in the motor domain causes dominant wing notching, indicating the importance of the motor activity. Klp64D shows subcellular localization to intracellular vesicles overlapping with Arm and Dsh. In klp64D mutants, Arm is abnormally accumulated in vesicular structures including Golgi, suggesting that intracellular trafficking of Arm is affected. Human KIF3A can also bind β-catenin and rescue klp64D RNAi phenotypes. Taken together, we propose that Klp64D is essential for Wg signaling by trafficking of Arm via the formation of a conserved complex with Arm.
authors: Department of Biological Sciences, Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science & Technology, Daejeon 305-701, Korea.
authors: Linh Thuong
authors: LT
authors: Vuong
authors: MedImmune, Gaithersburg, MD 20878, USA.
authors: Bibhash
authors: B
authors: Mukhopadhyay
authors: Department of Biological Sciences, Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science & Technology, Daejeon 305-701, Korea kchoi100@kaist.ac.kr.
authors: Kwang-Wook
authors: KW
authors: Choi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins / Q000502:physiology*; D019521:Body Patterning; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000502:physiology*; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014921:Wings, Animal / Q000196:embryology; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495305:ARM protein, Drosophila; D048868:Adaptor Proteins, Signal Transducing; D051186:Armadillo Domain Proteins; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; C087415:KIF3A protein, human; D010750:Phosphoproteins; D014157:Transcription Factors; D051176:beta Catenin; C000606588:dsh protein, Drosophila; C486143:KLP64D protein, Drosophila; D016547:Kinesins
keywords: Armadillo; Dishevelled; Drosophila kinesin II; Wingless/Wnt signaling