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  • Title: Beta-arrestin 2 regulates zebrafish development through the hedgehog signaling pathway.
    Author: Wilbanks AM, Fralish GB, Kirby ML, Barak LS, Li YX, Caron MG.
    Journal: Science; 2004 Dec 24; 306(5705):2264-7. PubMed ID: 15618520.
    Abstract:
    beta-arrestins are multifunctional proteins that act as scaffolds and transducers of intracellular signals from heptahelical transmembrane-spanning receptors (7TMR). Hedgehog (Hh) signaling, which uses the putative 7TMR, Smoothened, is established as a fundamental pathway in development, and unregulated Hh signaling is associated with certain malignancies. Here, we show that the functional knockdown of beta-arrestin 2 in zebrafish embryos recapitulates the many phenotypes of Hh pathway mutants. Expression of wild-type beta-arrestin 2, or constitutive activation of the Hh pathway downstream of Smoothened, rescues the phenotypes caused by beta-arrestin 2 deficiency. These results suggest that a functional interaction between beta-arrestin 2 and Smoothened may be critical to regulate Hh signaling in zebrafish development.
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