The non-canonical planar cell polarity (PCP) and Wnt-Ca2+ signaling pathways are relatively less well defined. In the Wnt/Ca2+ pathway, Wnt binding to Frizzled receptors results in the activation of heterotrimeric G proteins with subsequent mobilization of phospholipase C and phosphodiesterase. This induces a decrease in cGMP, a transient increase in intracellular Ca2+, and activation of protein kinase C (PKC), calcium calmodulin mediated kinase II (CAMKII), and the phosphatase calcineurin. Together these proteins promote cell migration and inhibit the canonical beta-Catenin-dependent signaling pathway.
In addition, Wnt can act through the PCP pathway to define polarity in select epithelial tissues, particularly along an axis perpendicular to the apical-basal border. Briefly, Wnt binding to Frizzled activates Dishevelled, likely on the C-terminus of the molecule. Dishevelled then recruits the RhoA and Rac GTPases, which ultimately activate Rho Kinases (ROCK) and c-jun NH2-terminal kinase (JNK). ROCK regulates actin cytoskeleton organization, smooth muscle contraction, and cell motility and adhesion, while JNK signaling activates the transcription factor AP-1.