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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 
 

Association of dishevelled with the clathrin ap-2 adaptor is required for frizzled endocytosis and planar cell polarity signaling.

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 mu2-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 mu2. Dvl2 mutants in the YHEL motif fail to associate with mu2 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.[1]

References

  1. Association of dishevelled with the clathrin ap-2 adaptor is required for frizzled endocytosis and planar cell polarity signaling. Yu, A., Rual, J.F., Tamai, K., Harada, Y., Vidal, M., He, X., Kirchhausen, T. Dev. Cell (2007) [Pubmed]
 
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