Dishevelled: The hub of Wnt signaling

Wnt signaling controls a variety of developmental and homeostatic events. As a key component of Wnt signaling, Dishevelled (Dvl/Dsh) protein relays Wnt signals from receptors to downstream effectors. In the canonical Wnt pathway that depends on the nuclear translocation of beta-catenin, DO is recruited by the receptor Frizzled and prevents the constitutive destruction of cytosolic beta-catenin. In the non-canonical Writ pathways such as Wnt-Frizzled/PCP (planar cell polarity) signaling, DO signals via the Daam1-RhoA axis and the Rac1 axis. In addition, DO plays important roles in Wnt-GSK3 beta-microtubule signaling, Wnt-calcium signaling, Wnt-RYK signaling, Wnt-atypical PKC signaling, etc. Dvl also functions to mediate receptor endocytosis. To fulfill its multifaceted functions, it is not surprising that DO associates with various kinds of proteins. Its activity is also modulated dynamically by phosphorylation, ubiquitination and degradation. In this review, we summarize the current understanding of DO functions in Wnt signal transduction and its biological functions in mouse development, and also discuss the molecular mechanisms of its actions. (C) 2009 Elsevier Inc. All rights reserved.