Abstract
Wnt proteins transmit myriad intercellular signals crucial for the development and homeostasis of metazoan animals from Hydra to human. Abnormal Wnt signaling causes a growing number of diseases, including cancer and osteoporosis. Depending on the context, a given Wnt signal may denote: cell proliferation or apoptosis; cell fate determination, differentiation, or stem cell maintenance; a variety of changes in cell behavior; and/or coordinated interactions with its neighbors. Which event(s) occur in Wnt-responsive cells depends critically on the ability of Dishevelled (Dsh)/Dvl proteins to interpret distinct types of intracellular, receptor-generated stimuli and transmit them to at least two distinct sets of effector molecules, all while apparently ignoring a third type of Wnt-generated Ca(2+) signal. The three conserved domains present in Dsh/Dvl proteins uniquely function in each Wnt pathway, in part by association with 18 (and counting) Dsh/Dvl-associated proteins. The latest data suggest that Dsh/Dvl proteins organize dynamic, pathway-specific subcellular signaling complexes that ensure correct information routing, signal amplification, and dynamic control through feedback regulation. The biochemical and cell biological mechanisms by which Dsh/Dvl proteins accomplish these remarkable tasks remain obscure.
