Beta-catenin-independent Wnt pathways: signals, core proteins, and effectors

Wnt signaling activates several distinct intracellular pathways, which are important for cell proliferation, differentiation, and polarity. Wnt proteins are secreted molecules that typically signal across the membrane via interaction with the transmembrane receptor Frizzled. Following interaction with Frizzled, the downstream effect of the most widely studied Wnt pathway is stabilization and nuclear translocation of the cytosolic protein, beta-catenin. In this chapter, we discuss two beta-catenin-independent branches of Wnt signaling: 1) Wnt/planar cell polarity (PCP), a Wnt pathway that signals through the small GTPases, Rho and Rac, to promote changes in the actin cytoskeleton, and 2) Wnt/Ca2+, a Wnt pathway that promotes intracellular calcium transients and negatively regulates the Wnt/beta-catenin pathway. Finally, during the course of our discussion, we highlight areas that require future research.