Editors' ChoiceReceptors

Frizzled Proteins Find G Proteins

STKE  05 Jun 2001:
Vol. 2001, Issue 85, pp. tw4
DOI: 10.1126/stke.2001.85.tw4

Wnt proteins play critical roles in the control of development, and appear to act by binding to receptors known as Frizzled proteins. Although the Frizzled proteins look like G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors, there is little evidence to support such a signaling mechanism. Analysis of the receptor function has been limited by the lack of availability of purified Wnt ligands. Liu et al. have created a chimeric Frizzled receptor in which the extracellular and transmembrane domains of the hamster β2-adrenergic receptor (β2AR) were fused to the intracellular domain of rat Frizzled-1. Mouse F9 teratocarcinoma cells expressing the modified receptor then responded to the β2AR agonist isoprenaline as though they had been treated with Wnt. They showed typical stabilization of β-catenin, which then acts in the nucleus to promote transcription of Wnt-regulated genes in cooperation with the TCF and LEF transcription factors. In cultured animal caps from Xenopus embryos, pertussis toxin (an inhibitor of G protein signaling) blocked the transcriptional response to transfected Wnt8. Together, the results indicate that Frizzled proteins do indeed produce their classic developmental effects through β-catenin and TCF-LEF by coupling to G proteins.

T. Liu, A. J. DeCostanzo, X. Liu, H.-y. Wang, S. Hallagan, R. T. Moon, C. C. Malbon, G protein signaling from activated rat Frizzled-1 to the β-catenin-Lef-Tcf pathway. Science 292, 1718-1722 (2001). [Abstract] [Full Text]