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Semin Cell Dev Biol. 2014 Sep;33:63-72. doi: 10.1016/j.semcdb.2014.05.002. Epub 2014 May 17.

G-protein-coupled receptors, Hedgehog signaling and primary cilia.

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Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address:
Department of Medicine, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA. Electronic address:


The Hedgehog (Hh) pathway has become an important model to study the cell biology of primary cilia, and reciprocally, the study of ciliary processes provides an opportunity to solve longstanding mysteries in the mechanism of vertebrate Hh signal transduction. The cilium is emerging as an unique compartment for G-protein-coupled receptor (GPCR) signaling in many systems. Two members of the GPCR family, Smoothened and Gpr161, play important roles in the Hh pathway. We review the current understanding of how these proteins may function to regulate Hh signaling and also highlight some of the critical unanswered questions being tackled by the field. Uncovering GPCR-regulated mechanisms important in Hh signaling may provide therapeutic strategies against the Hh pathway that plays important roles in development, regeneration and cancer.


G-protein coupled receptors; Hedgehog; Primary cilia; Protein Kinase A

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