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Trends Cell Biol. 2010 May;20(5):287-98. doi: 10.1016/j.tcb.2010.02.002. Epub 2010 Mar 5.

Evaluating Smoothened as a G-protein-coupled receptor for Hedgehog signalling.

Author information

1
Institute of Developmental Biology and Cancer, CNRS UMR6543, Université Nice - Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.

Abstract

The Hedgehog signalling pathway controls numerous developmental processes. In response to Hedgehog, Smoothened (Smo), a seven-pass transmembrane protein, orchestrates pathway signalling and controls transcription factor activation. In the absence of Hedgehog, the receptor Patched indirectly inhibits Smo in a catalytic manner. Many questions surrounding Smo activation and signalling remain. Recent findings in Drosophila and vertebrate systems have provided strong evidence that Smo acts as a G-protein-coupled receptor. We discuss the role and regulation of Smo and reassess similarities between Smo and G-protein-coupled receptors. We also examine recently identified members of the invertebrate and vertebrate Smo signalling cascades that are typical components of G-protein-coupled receptor pathways. Greater understanding of the mechanisms of Smo activation and its signalling pathways will allow implementation of novel strategies to target disorders related to disruption of Hh signalling.

PMID:
20207148
DOI:
10.1016/j.tcb.2010.02.002
[Indexed for MEDLINE]

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