Smoothened Adopts Multiple Active and Inactive Conformations Capable of Trafficking to the Primary Cilium

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Apr 15

PMID 19365551

Citations 63

Authors

Christopher W Wilson

Miao-Hsueh Chen

Pao-Tien Chuang

Affiliations

Soon will be listed here.

Abstract

Activation of Hedgehog (Hh) signaling requires the transmembrane protein Smoothened (Smo), a member of the G-protein coupled receptor superfamily. In mammals, Smo translocates to the primary cilium upon binding of Hh ligands to their receptor, Patched (Ptch1), but it is unclear if ciliary trafficking of Smo is sufficient for pathway activation. Here, we demonstrate that cyclopamine and jervine, two structurally related inhibitors of Smo, force ciliary translocation of Smo. Treatment with SANT-1, an unrelated Smo antagonist, abrogates cyclopamine- and jervine-mediated Smo translocation. Further, activation of protein kinase A, either directly or through activation of Galphas, causes Smo to translocate to a proximal region of the primary cilium. We propose that Smo adopts multiple inactive and active conformations, which influence its localization and trafficking on the primary cilium.

Citing Articles

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