Research ArticleDevelopmental Biology

G protein–coupled receptors control the sensitivity of cells to the morphogen Sonic Hedgehog

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Sci. Signal.  06 Feb 2018:
Vol. 11, Issue 516, eaao5749
DOI: 10.1126/scisignal.aao5749

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GPCRs reduce sensitivity to Sonic Hedgehog

In the developing spinal cord, Sonic Hedgehog (SHH) released from the notochord and floor plate induces overlying neural progenitor cells (NPCs) to differentiate into different neural cell types in a concentration-dependent manner. Pusapati et al. found that loss of the G protein–coupled receptor (GPCR) GPR161 sensitized both cultured fibroblasts and NPCs to SHH. The ability of Gαs, which is activated by GPR161, to negatively regulate SHH signaling did not strictly depend on GPR161, suggesting that other GPCRs that couple to Gαs may also attenuate SHH signaling. Although GPCR kinase 2 (GRK2) is proposed to promote SHH signaling by removing GPR161 from the primary cilium, the authors found that GRK2 enhanced SHH signaling independently of GPR161. GRK2, GPR161, and Gαs tuned cellular sensitivity to SHH likely by affecting the extent of protein kinase A activity, a negative regulator of SHH signaling (see also Focus by Sharpe and de Sauvage).