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Question

What is the function of the Smoothened (Smo) receptor in the Hedgehog signaling pathway?

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Explanation

Smoothened is seven-transmembrane protein homologous to G protein-coupled receptors, acting as obligate transducer of Hedgehog signaling downstream of Patched. In absence of Hedgehog, Patched twelve-pass transporter inhibits Smoothened by preventing ciliary accumulation, promoting cholesterol transport imbalance and internalization. Hedgehog binding to Patched via lipoprotein particles relieves inhibition, allowing Smoothened to translocate to primary cilium tip, activate heterotrimeric Gi proteins, suppress Sufu-Gli sequestration, leading to Gli activator formation. It does not directly bind ligand but transduces signal intracellularly essential for pathway activation, patterning neural tube and limb.

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