spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

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

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.02217v1
133/3/471    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Callejo, A.
Right arrow Articles by Guerrero, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Callejo, A.
Right arrow Articles by Guerrero, I.

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.


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
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]

Home page
 GeneticsHome page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 DevelopmentHome page
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]

Home page
 J. Cell Sci.Home page
M. Varjosalo and J. Taipale
Hedgehog signaling
J. Cell Sci., January 1, 2007; 120(1): 3 - 6.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 DevelopmentHome page
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