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Published online
doi:10.1083/jcb.200907126
The Journal of Cell Biology, Vol. 187, No. 3, 365-374
The Rockefeller University Press, 0021-9525 $30.00
© Milenkovic et al.
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Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium



Ljiljana Milenkovic1, Matthew P. Scott1, and Rajat Rohatgi2

Howard Hughes Medical Institute, 1 Department of Developmental Biology, 1 Department of Genetics, 1 Department of Bioengineering, 1 Department of Medicine, 2 and Department of Biochemistry, 2 Stanford University School of Medicine, Stanford, CA 94305

Correspondence to Rajat Rohatgi: rrohatgi{at}stanford.edu; and Matthew P. Scott: mscott{at}stanford.edu

The function of primary cilia depends critically on the localization of specific proteins in the ciliary membrane. A major challenge in the field is to understand protein trafficking to cilia. The Hedgehog (Hh) pathway protein Smoothened (Smo), a 7-pass transmembrane protein, moves to cilia when a ligand is received. Using microscopy-based pulse-chase analysis, we find that Smo moves through a lateral transport pathway from the plasma membrane to the ciliary membrane. Lateral movement, either via diffusion or active transport, is quite distinct from currently studied pathways of ciliary protein transport in mammals, which emphasize directed trafficking of Golgi-derived vesicles to the base of the cilium. We anticipate that this alternative route will be used by other signaling proteins that function at cilia. The path taken by Smo may allow novel strategies for modulation of Hh signaling in cancer and regeneration.

Abbreviations used in this paper: CBG, C8 propanoic acid benzylguanine; DIP, dynamin inhibitory peptide; Fsk, Forskolin; Hh, Hedgehog; Ptc1, Patched 1; SAG, Smo agonist; Smo, Smoothened; Shh, Sonic hedgehog.

© 2009 Milenkovic et al.
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