Abstract
Upon activation by Wnt, the Frizzled receptor is internalized in a process that requires the recruitment of Dishevelled. We describe a novel interaction between Dishevelled2 (Dvl2) and μ2-adaptin, a subunit of the clathrin adaptor AP-2; this interaction is required to engage activated Frizzled4 with the endocytic machinery and for its internalization. The interaction of Dvl2 with AP-2 requires simultaneous association of the DEP domain and a peptide YHEL motif within Dvl2 with the C terminus of μ2. Dvl2 mutants in the YHEL motif fail to associate with μ2 and AP-2, and prevent Frizzled4 internalization. Corresponding Xenopus Dishevelled mutants show compromised ability to interfere with gastrulation mediated by the planar cell polarity (PCP) pathway. Conversely, a Dvl2 mutant in its DEP domain impaired in PCP signaling exhibits defective AP-2 interaction and prevents the internalization of Frizzled4. We suggest that the direct interaction of Dvl2 with AP-2 is important for Frizzled internalization and Frizzled/PCP signaling.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 129-141 |
| Number of pages | 13 |
| Journal | Developmental Cell |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2007 |
Funding
We thank Drs. W. Boll and I. Rapoport for supplying us with clathrin adaptors, and the members of our laboratories for helpful discussions. We also thank Dr. M. Asashima for the Xenopus pCS2+ vector encoding c-Jun, and Dr. M. Semenov for the antibodies specific for Dvl2. The data presented in Figure 6 were generated by K. Tamai and Y. Harada. This work was supported by National Institutes of Health grants GM036548 (T.K) and GM074241 (X.H.). X.H. is a W.M. Keck Foundation Distinguished Young Scholar and a Lymphoma and Leukemia Society Scholar.
Keywords
- CELLBIO
- SIGNALING
ASJC Scopus subject areas
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- Developmental Biology
- Cell Biology