Gain-of-function Shh mutants activate Smo cell-autonomously independent of Ptch1/2 function

Publication date: Available online 23 August 2018Source: Mechanisms of DevelopmentAuthor(s): Catalina Casillas, Henk RoelinkAbstractSonic Hedgehog (Shh) signaling is characterized by non-cell autonomy; cells expressing Shh do not respond to the ligand. Here, we identify several Shh mutations that can activate the Hedgehog (Hh) pathway cell-autonomously. Cell-autonomous pathway activation requires the extracellular cysteine rich domain of Smoothened, but is otherwise independent of the Shh receptors Patched1 and -2. Many of the Shh mutants that gain activity fail to undergo auto processing resulting in the perdurance of the Shh pro-peptide, a form of Shh that is sufficient to activate the Hh response cell-autonomously. Our results demonstrate that Shh is capable of activating the Hh pathway via Smoothened, independently of Patched1/2, and that it harbors an intrinsic mechanism that prevents cell-autonomous activation of the Shh response.

Source: Mechanisms of Development - August 23, 2018 Category: Biology Source Type: research