Receptor Activation

Alternate Path to Smo

Science's STKE  27 Aug 2002:
Vol. 2002, Issue 147, pp. tw313-TW313
DOI: 10.1126/stke.2002.147.tw313

The soluble factor Hedgehog (Hh) regulates cell growth and embryonic patterning by activating a cell-surface receptor called Smoothened (Smo). It is thought that Smo is kept inactivated through its association with another transmembrane protein called Patched (Ptc) and that binding of Hh to Ptc relieves Smo inhibition. However, Taipale et al. propose that regulation of this stoichiometric Ptc-Smo relationship may not necessarily underlie Smo activation. The authors show that substoichiometric expression levels of Ptc can regulate Smo. They also found that Smo and Ptc did not colocalize in mammalian cells. It remains unclear how Ptc catalyzes Smo suppression, but the authors detected some similarity between Ptc and a bacterial transmembrane transporter. They suggest that in the absence of Hh, Ptc could translocate a small molecule that either directly or indirectly inhibits Smo.

J. Taipale, M. K. Cooper, T. Maiti, P. A. Beachy, Patched acts catalytically to suppress the activity of Smoothened. Nature 418, 892-897 (2002). [Online Journal]