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Association of Dishevelled with the Clathrin AP-2 Adaptor Is Required for Frizzled Endocytosis and Planar Cell Polarity Signaling. Yu A. et al, Developmental cell (2007). Wnt signaling and Endocytosis.
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Association of Dishevelled with the Clathrin AP-2 Adaptor Is Required for Frizzled Endocytosis and Planar Cell Polarity Signaling Yu A. et al, Developmental cell (2007)
Wnt signaling and Endocytosis • Regulated endocytic routing modulates wingless signaling in Drosophila embryos (Dubois L. et al, 2001) • Internalization is required for proper Wingless signaling in Drosophila melanogaster (Seto E.S. and Bellen H.J., 2006) • Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4(Chen W. et al, 2003) • Wnt proteins are rapidly endocytosed by a clathrin- and dynamin- mediated process (Blitzer J.T. and Nusse R., 2006) • Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of beta-catenin (Yamammoto H. et al, 2006)
Clathrin and Adaptor proteins(Aps) • two large chains, of molecular weights 100 kDa, and two smaller chains, of 50 and 20 kDa • APs interact with clathrin, cargo, and regulatory proteins, and probably have pivotal roles in coat assembly Rappoport J.Z. et al, Traffic (2004)
AP-2 AP-3 AP-1 Robinson M.S., TRENDS in Cell Biology (2004)
Traub L.M., J.C.B. (2007) Spiegel A., SCIENCE (2003)
Specific Interaction of Dishevelled with the C-Terminal Domain of μ-Adaptins of Clathrin Adaptors
Association of Mammalian Dishevelled Proteins with Heterotetrameric Clathrin Adaptor Complexes COS7 cell – lack endogenous b-arrestin2
Mapping of the Region within Dvl2 Required to Associate with AP-2 Residue – 566~589 Residue – 408~507 (DEP domain)
The DEP Domain and the YHEL Motif of Dvl2 Are Required for its Efficient Association with AP-2
Expression of Dvl2 AHEL or of Dvl2 K446M Prevents the Internalization of Activated Frizzled4
Ectopic expression of Xdsh with mutations results in stabilization of β-catenin and axis duplication
The YHEL Motif in Xdsh Is Involved in PCP Signaling and Xenopus Gastrulation Wallingford J.B., Development (2001)