Abstract
Wnt proteins, regulators of development in many organisms, bind to seven transmembrane-spanning (7TMS) receptors called frizzleds, thereby recruiting the cytoplasmic molecule dishevelled (Dvl) to the plasma membrane.Frizzled-mediated endocytosis of Wg (a Drosophila Wnt protein) and lysosomal degradation may regulate the formation of morphogen gradients. Endocytosis of Frizzled 4 (Fz4) in human embryonic kidney 293 cells was dependent on added Wnt5A protein and was accomplished by the multifunctional adaptor protein beta-arrestin 2 (betaarr2), which was recruited to Fz4 by binding to phosphorylated Dvl2. These findings provide a previously unrecognized mechanism for receptor recruitment of beta-arrestin and demonstrate that Dvl plays an important role in the endocytosis of frizzled, as well as in promoting signaling.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Arrestins / genetics
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Arrestins / metabolism*
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Cell Line
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Cell Membrane / metabolism
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Clathrin / metabolism
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Cytoplasm / metabolism
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Dishevelled Proteins
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Drosophila Proteins
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Endocytosis*
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Frizzled Receptors
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Humans
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Mice
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins / pharmacology
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RNA, Small Interfering
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Wnt Proteins
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Wnt-5a Protein
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beta-Arrestin 2
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beta-Arrestins
Substances
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ARRB2 protein, human
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Adaptor Proteins, Signal Transducing
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Arrb2 protein, mouse
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Arrestins
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Clathrin
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DVL2 protein, human
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Dishevelled Proteins
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Drosophila Proteins
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Dvl2 protein, mouse
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Frizzled Receptors
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Recombinant Fusion Proteins
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Wnt Proteins
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Wnt-5a Protein
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Wnt5a protein, mouse
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beta-Arrestin 2
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beta-Arrestins
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dsh protein, Drosophila
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Protein Kinase C