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Sci. Signal., 21 August 2012
Vol. 5, Issue 238, p. ra60
Signaling Move from Outside the Cilium
Hedgehog (Hh) can trigger transcriptional responses that control differentiation or it can stimulate chemotaxis or axonal pathfinding. The transcriptional response to Hh requires trafficking of the receptor Smoothened (Smo) to the primary cilium. Bijlsma et al. showed that cells expressing mutants of Smo that could not traffic to the primary cilium or cells lacking components needed for maintenance of the primary cilium exhibited a robust Smo-mediated chemotactic response, but failed to exhibit a transcriptional response. Cells expressing mutants that could not traffic to the primary cilium showed an enhanced chemotactic response. The intracellular trafficking of Smo was altered in the absence of the primary cilium or for Smo mutants without the ability to target to the cilium. Experiments with pharmacological inhibitors indicated that pertussis toxin–sensitive G proteins and autocrine leukotriene signaling contributed to the chemotactic response. Thus, Hh can stimulate a chemotactic or transcriptional response, which depends on the intracellular trafficking of Smo and involves distinct signaling pathways.
Citation: M. F. Bijlsma, H. Damhofer, H. Roelink, Hedgehog-Stimulated Chemotaxis Is Mediated by Smoothened Located Outside the Primary Cilium. Sci. Signal.5, ra60 (2012).