Beta-arrestin-mediated localization of smoothened to the primary cilium.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kovacs, JJ; Whalen, EJ; Liu, R; Xiao, K; Kim, J; Chen, M; Wang, J; Chen, W; Lefkowitz, RJ

Published Date

  • June 27, 2008

Published In

Volume / Issue

  • 320 / 5884

Start / End Page

  • 1777 - 1781

PubMed ID

  • 18497258

Pubmed Central ID

  • 18497258

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1157983

Language

  • eng

Conference Location

  • United States