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

Abstract:

: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.

journal_name

Cell

journal_title

Cell

authors

Lewis PM,Dunn MP,McMahon JA,Logan M,Martin JF,St-Jacques B,McMahon AP

doi

10.1016/s0092-8674(01)00369-5

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

599-612

issue

5

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(01)00369-5

journal_volume

105

pub_type

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