Jun 8, 2001

Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1

P M LewisA P McMahon


Sonic hedgehog (Shh) signaling from the posterior zone of polarizing activity (ZPA) is the primary determinant of anterior-posterior polarity in the vertebrate limb field. An active signal is produced by an autoprocessing reaction that covalently links cholesterol to the N-terminal signaling moiety (N-Shh(p)), tethering N-Shh(p) to the cell membrane. We have addressed the role played by this lipophilic modification in Shh-mediated patterning of mouse digits. Both the distribution and activity of N-Shh(p) indicate that N-Shh(p) acts directly over a few hundred microns. In contrast, N-Shh, a form that lacks cholesterol, retains similar biological activity to N-Shh(p), but signaling is posteriorly restricted. Thus, cholesterol modification is essential for the normal range of signaling. It also appears to be necessary for appropriate modulation of signaling by the Shh receptor, Ptc1.

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Mentioned in this Paper

Hedgehog Proteins
Transforming Growth Factor beta
Bone morphogenetic protein 4
Intracellular Signaling Proteins
Hormone Receptors, Cell Surface
PTCH1 wt Allele
GLI Family Protein
Gene Products, Protein

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