Location, Location, Location

Abstract

Despite substantial effort, it has remained relatively mysterious how the protein known as Hedgehog (Hh) activates signaling pathways that regulate various biological processes, including stem cell function, development, and cancer. Rohatgi et al . (see the Perspective by Christensen and Ott) show that mammalian cells use their primary cilium as an antenna that samples the surrounding environment for the presence of Hh. When Hh bound to its receptor Patched 1 (Ptc1), the receptor left the cilia, where (in the absence of stimulation) it acts to restrain Hh signaling by preventing accumulation of the signaling protein Smoothened (Smo). Accumulation of Smo in the cilia of stimulated cells corresponded to activation of Hh signaling. Further understanding the molecular mechanisms that influence cellular localization of Ptc1 and Smo will improve understanding of the signaling pathway and may lead to new therapeutic targets. R. Rohatgi, L. Milenkovic, M. P. Scott, Patched1 regulates Hedgehog signaling at the primary cilium. Science 317 , 372-376 (2007). [Abstract] [Full Text] S. T. Christensen, C. M. Ott, A ciliary signaling switch. Science 317 , 330-331 (2007). [Summary] [Full Text]