Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Chen, W; ten Berge, D; Brown, J; Ahn, S; Hu, LA; Miller, WE; Caron, MG; Barak, LS; Nusse, R; Lefkowitz, RJ
Published Date
- September 5, 2003
Published In
Volume / Issue
- 301 / 5638
Start / End Page
- 1391 - 1394
PubMed ID
- 12958364
Electronic International Standard Serial Number (EISSN)
- 1095-9203
Digital Object Identifier (DOI)
- 10.1126/science.1082808
Language
- eng
Conference Location
- United States