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Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4.

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.

Pubmed ID: 12958364

Authors

  • Chen W
  • ten Berge D
  • Brown J
  • Ahn S
  • Hu LA
  • Miller WE
  • Caron MG
  • Barak LS
  • Nusse R
  • Lefkowitz RJ

Journal

Science (New York, N.Y.)

Publication Data

September 5, 2003

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL 16037
  • Agency: NHLBI NIH HHS, Id: HL 61365
  • Agency: NINDS NIH HHS, Id: NS 19576

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Arrestins
  • Cell Line
  • Cell Membrane
  • Clathrin
  • Cytoplasm
  • Endocytosis
  • Frizzled Receptors
  • Humans
  • Mice
  • Phosphoproteins
  • Phosphorylation
  • Protein Kinase C
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Signal Transduction
  • Wnt Proteins