Wnt Signaling Through Transducins

Science's STKE  10 Dec 2002:
Vol. 2002, Issue 162, pp. tw465-TW465
DOI: 10.1126/stke.2002.162.tw465

Wnts are signaling molecules with critical roles in development that act though a receptor called Frizzled. Although Frizzled proteins resemble heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors, Wnt signaling is best understood in cases where Wnt's control transcription through a β-catenin-dependent signaling mechanism. Ahumada et al. describe a different mechanism for Wnt signaling, in which the rat Frizzled-2 protein appears to be coupled to the G protein transducin, which is better known for its central role in signaling in visual tissues that respond to light. In cultured cells, activation of transducin was required for Wnt-dependent activation of guanosine 3',5'-monophosphate (cGMP)-dependent phosphodiesterase, as well as for subsequent decreases in the intracellular concentration of cGMP and increased release of calcium from intracellular stores. Wnt signaling during zebrafish gastrulation could be inhibited when phosphodiesterase activity was reduced after application of pharmacological inhibitors.

A. Ahumada, D. C. Slusarski, X. Liu, R. T. Moon, C. C. Malbon, H. Wang, Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP. Science 298, 2006-2010 (2002). [Abstract] [Full Text]