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

Lewis, P. M., Dunn, M. P., McMahon, J. A., Logan, M., Martin, J. F., St-Jacques, B., McMahon, A. P. (June 2001) Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1. Cell, 105 (5). pp. 599-612. ISSN 0092-8674 (Print)0092-8674

URL: https://www.ncbi.nlm.nih.gov/pubmed/11389830
DOI: 10.1016/S0092-8674(01)00369-5

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.

Item Type: Paper
Subjects: organism description > animal > developmental stage > limb development
organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction
CSHL Authors:
Communities: CSHL Library and Archives
Depositing User: Matthew Dunn
Date: 1 June 2001
Date Deposited: 09 Jan 2019 21:25
Last Modified: 09 Jan 2019 21:25
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37658

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving