G-protein-coupled receptors, Hedgehog signaling and primary cilia.
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.
Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address: saikat.mukhopadhyay@utsouthwestern.edu.
Saikat
S
Mukhopadhyay
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: rrohatgi@stanford.edu.
Rajat
R
Rohatgi
D000818:Animals; D019521:Body Patterning; D002923:Cilia / Q000502:physiology*; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction
D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled
G-protein coupled receptors; Hedgehog; Primary cilia; Protein Kinase A