3ml6

Publication Abstract from PubMed

Wnt association with its receptor, Frizzled (Fz), and recruitment by the latter of an adaptor, Dishevelled (Dvl), initiates signaling through at least two distinct pathways ("canonical" and "noncanonical"). Endocytosis and compartmentalization help determine the signaling outcome. Our previous work has shown that Dvl2 links at least one Frizzled family member (Fz4) to clathrin-mediated endocytosis by interacting with the mu2 subunit of the AP-2 clathrin adaptor, through both a classical endocytic tyrosine motif and a so-called "DEP domain." We report here the crystal structure of a chimeric protein that mimics the Dvl2-mu2 complex. The DEP domain binds at one end of the elongated, C-terminal domain of mu2. This domain:domain interface shows that parts of the mu2 surface distinct from the tyrosine-motif site can help recruit specific receptors or adaptors into a clathrin coated pit. Mutation of residues at the DEP-mu2 contact or in the tyrosine motif reduce affinity of Dvl2 for mu2 and block efficient internalization of Fz4 in response to ligation by Wnt5a. The crystal structure has thus allowed us to identify the specific interaction that leads to Frizzled uptake and to downstream, noncanonical signaling events.

Structural analysis of the interaction between Dishevelled2 and clathrin AP-2 adaptor, a critical step in noncanonical Wnt signaling.,Yu A, Xing Y, Harrison SC, Kirchhausen T Structure. 2010 Oct 13;18(10):1311-20. PMID:20947020^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.