Sci. STKE, 18 October 2005
CELL BIOLOGY Ciliary Signaling
Most vertebrate cells have a primary cilium. Recent evidence indicates that, unlike the cilia of unicellular organisms that confer motility, those on vertebrate cells may be waving about in the extracellular environment picking up signals. In mice, mutations that prevent cilia formation produce developmental defects similar to those in animals with disrupted Hedgehog signaling. Corbit et al. now report that Smoothened proteins (Smo), which are receptors for the morphogen Hedgehog, could be detected on cells of the ventral node of three-somite-stage mouse embryos, especially on the primary cilium. Such localization of Smo was enhanced in various cultured cells treated with an activating ligand for Smo and was lost in cells treated with a Smo antagonist. The authors used mutants lacking key residues in a motif required for ciliary localization to show that activation of a reporter gene in cells transfected with the receptor required localization of Smo to the cilium. Similarly, such mutant Smo molecules were unable to rescue morphological defects in Zebrafish embryos lacking endogenous Smo. Precisely why Smo needs to be at the cilium to function remains to be explored. The authors suggest that it may need to be there to interact with an activator or that signaling complexes formed with other components of the Hedgehog signaling pathway may also accumulate at the cilium.
K. C. Corbit, P. Aanstad, V. Singla, A. R. Norman, D. Y. R. Stainier, J. F. Reiter, Vertebrate Smoothened functions at the primary cilium. Nature 437, 1018-1021 (2005). [PubMed]
Citation: Ciliary Signaling. Sci. STKE 2005, tw369 (2005).
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