Channeling hedgehogs

The Hedgehog (Hh) signaling pathway strikes again. The framework of the pathway is simple enough: Hh binds to its receptor Patched (Ptc), thus relieving Ptc inhibition of Smoothened (Smo) signaling. But now Jussi Taipale, Philip Beachy, and colleagues (Johns Hopkins University, Baltimore, MD) have found that Ptc may act as a channel.

This is not the first strange episode in Hh biology. Hh looks like a bacterial cell wall protein, and uses a bizarre mechanism related to that of self-splicing proteins to attach cholesterol to itself. “This signaling pathway, which has very profound roles in multicellular organisms, was very clearly put together with bits of this and that,” says Beachy. “At this point, nothing surprises us.”

Ptc was thought to be a conventional receptor that gripped Smo in an inhibitory embrace. But Taipale suspected that...