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

Jeffrey J Kovacs1, Erin J Whalen, Renshui Liu

  • 1Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Science (New York, N.Y.)
|May 24, 2008
PubMed

Insights

Beta-arrestins facilitate the transport of Smoothened (Smo), a seven-transmembrane receptor (7TMR), to primary cilia. This process is crucial for Hedgehog pathway signaling and Gli transcription factor activation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Beta-arrestins regulate seven-transmembrane receptors (7TMRs).
  • Smoothened (Smo), a 7TMR, is vital for Hedgehog signaling in development and implicated in tumorigenesis.
  • Smo signaling in mammalian cells necessitates its translocation to primary cilia.

Purpose of the Study:

  • To investigate the role of beta-arrestins in Smo trafficking and signaling.
  • To elucidate the mechanism by which beta-arrestins mediate Smo localization to primary cilia.

Main Methods:

  • Utilized small interfering RNA (siRNA) to deplete beta-arrestin 1 or 2.
  • Examined the localization of Smo and its interaction with Kif3A in primary cilia.
  • Assessed Smo-dependent Gli transcription factor activation.

Main Results:

  • Beta-arrestins mediate the interaction between Smo and the kinesin motor protein Kif3A.
  • This multimeric complex was found to localize to primary cilia.
  • Depletion of beta-arrestins disrupted Smo localization to primary cilia and blocked Smo-dependent Gli activation.

Conclusions:

  • Beta-arrestins are essential for the intracellular transport of Smo to primary cilia.
  • This transport is a prerequisite for Smo-dependent signaling via the Hedgehog pathway.
  • Beta-arrestins play a critical role in regulating 7TMR localization for proper cellular function.

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