β-arrestin-mediated localization of smoothened to the primary cilium

beta-arrestins have important roles in the regulation of seven- transmembrane receptors ( 7TMRs). Smoothened ( Smo) is a 7TMR that mediates effects of Hedgehog on developmental processes and whose dysregulation may cause tumorigenesis. beta-Arrestins are required for endocytosis of Smo and signaling to Gli transcription factors. In mammalian cells, Smo- dependent signaling requires translocation to primary cilia. We demonstrated that beta- arrestins mediate the activity- dependent interaction of Smo and the kinesin motor protein Kif3A. This multimeric complex localized to primary cilia and was disrupted in cells transfected with beta- arrestin small interfering RNA. beta- Arrestin 1 or beta- arrestin 2 depletion prevented the localization of Smo to primary cilia and the Smo- dependent activation of Gli. These results suggest roles for beta- arrestins in mediating the intracellular transport of a 7TMR to its obligate subcellular location for signaling.