The fully linked HTML version of this article has now been published.
Development ePress online publication date 5 Jan 2006
doi: 10.1242/dev.02217
Research article
Hedgehog lipid modifications are required for Hedgehog stabilization in the extracellular matrix
Ainhoa Callejo,
Carlos Torroja,
Luis Quijada,
and
Isabel Guerrero*
* Author for correspondence (e-mail: iguerrero{at}cbm.uam.es)
The Hedgehog (Hh) family of morphogenetic proteins has important instructional roles in metazoan development. Despite Hh being modified by Ct-cholesterol and Nt-palmitate adducts, Hh migrates far from its site of synthesis and programs cellular outcomes, depending on its local concentrations. We show that in the receiving cells of the Drosophila wing imaginal disc, lipid-unmodified Hh spreads across many more cell diameters than the wild type and this spreading leads to the activation of low but not high threshold responses. Unlipidated Hh forms become internalized through the apical plasma membrane, while wild-type Hh enters through the basolateral cell surface - in all cases via a dynamin-dependent mechanism. Full activation of the Hh pathway and the spread of Hh throughout the extracellular matrix depend on the ability of lipid-modified Hh to interact with heparan sulfate proteoglycans (HSPG). However, neither Hh-lipid modifications nor HSPG function are required to activate the targets that respond to low levels of Hh. All these data show that the interaction of lipid-modified Hh with HSPG is important both for precise Hh spreading through the epithelium surface and for correct Hh reception.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Yan and X. Lin
Shaping Morphogen Gradients by Proteoglycans
Cold Spring Harb Perspect Biol,
September 1, 2009;
1(3):
a002493 - a002493.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Varjosalo and J. Taipale
Hedgehog: functions and mechanisms
Genes & Dev.,
September 15, 2008;
22(18):
2454 - 2472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Buglino and M. D. Resh
Hhat Is a Palmitoylacyltransferase with Specificity for N-Palmitoylation of Sonic Hedgehog
J. Biol. Chem.,
August 8, 2008;
283(32):
22076 - 22088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Casso, S. Liu, D. D. Iwaki, S. K. Ogden, and T. B. Kornberg
A Screen for Modifiers of Hedgehog Signaling in Drosophila melanogaster Identifies swm and mts
Genetics,
March 1, 2008;
178(3):
1399 - 1413.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Callejo, J. Culi, and I. Guerrero
Patched, the receptor of Hedgehog, is a lipoprotein receptor
PNAS,
January 22, 2008;
105(3):
912 - 917.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Huang, Y. Litingtung, and C. Chiang
Region-specific requirement for cholesterol modification of sonic hedgehog in patterning the telencephalon and spinal cord
Development,
June 1, 2007;
134(11):
2095 - 2105.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Varjosalo and J. Taipale
Hedgehog signaling
J. Cell Sci.,
January 1, 2007;
120(1):
3 - 6.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. McLellan, S. Yao, X. Zheng, B. V. Geisbrecht, R. Ghirlando, P. A. Beachy, and D. J. Leahy
From the Cover: Structure of a heparin-dependent complex of Hedgehog and Ihog
PNAS,
November 14, 2006;
103(46):
17208 - 17213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Wendler, X. Franch-Marro, and J.-P. Vincent
How does cholesterol affect the way Hedgehog works?
Development,
August 15, 2006;
133(16):
3055 - 3061.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2006
