Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium.
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.
Milenkovic
Ljiljana
L
Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Scott
Matthew P
MP
Rohatgi
Rajat
R
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D034281:Dynamins / Q000502:physiology; D004705:Endocytosis; D053823:Hedgehog Proteins / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D021381:Protein Transport / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D000072086:Smoothened Receptor
D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; C465570:Shh protein, mouse; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D034281:Dynamins