Patched1 Regulates Hedgehog Signaling at the Primary Cilium

TLDR

Primary cilia are essential for transducing Hedgehog signaling in mammals. The study examined how primary cilia regulate the Hedgehog receptor Patched1. Binding of Shh to Patched1 causes the receptor to exit cilia, allowing Smoothened to accumulate and activate signaling. Patched1 resides in cilia and blocks Smoothened accumulation, and cilia‑mediated Hedgehog signaling is crucial for development, cancer, and stem cell biology.

Abstract

Primary cilia are essential for transduction of the Hedgehog (Hh) signal in mammals. We investigated the role of primary cilia in regulation of Patched1 (Ptc1), the receptor for Sonic Hedgehog (Shh). Ptc1 localized to cilia and inhibited Smoothened (Smo) by preventing its accumulation within cilia. When Shh bound to Ptc1, Ptc1 left the cilia, leading to accumulation of Smo and activation of signaling. Thus, primary cilia sense Shh and transduce signals that play critical roles in development, carcinogenesis, and stem cell function.