Dishevelled: A Mobile Scaffold Catalyzing Development

Wnt proteins are secreted glycoprotein ligands that regulate critical aspects of development, including cell proliferation, apoptosis, and cell fate. For those pathways downstream from the "canonical" Wnt/beta-catenin signaling, from the "non-canonical" or planar cell polarity (PCP), and from the Wnt-Ca²⁺/cyclic guanosine monophosphate (cGMP) pathway, Wnt activation of its cellular receptor, a member of the superfamily of G-protein-coupled receptor Frizzled family, requires both heterotrimeric G proteins and the phosphoprotein Dishevelled. Our understanding of the roles of Dishevelled proteins in development is evolving and most recent observations suggest that Dishevelled proteins act as scaffolds essential for Wnt signaling, providing docking sites for a diverse and interesting set of protein kinases, phosphatases, adaptor proteins, G proteins, and other scaffolds such as Axin. The protein-protein interactions of Dishevelled are dynamic, as is the spatial localization of this "toolbox" of signaling molecules involved in development. Much excitement awaits the elucidation of the complete set of tools in the toolbox and of the dynamic regulation of Dishevelled proteins and their interacting proteins.