| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 279, Issue 32, 33220-33227, August 6, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, Massachusetts 01003
Wnt signaling pathways regulate many developmental responses; however, little is known about how Wnt ligands function on a biochemical level. Recent studies have shown that Wnt-3a is palmitoylated before secretion. Here we report that Drosophila Wnt-1 (Wingless) also undergoes a lipid modification. Lipidation occurs in the endoplasmic reticulum and is dependent on Porcupine, a putative O-acyltransferase. After modification, DWnt-1 partitions as a membrane-anchored protein and is sorted into lipid raft detergent-insoluble microdomains. Lipidation, raft targeting, and secretion can be blocked by the addition of 2-bromopalmitate, a competitive inhibitor of O-acyltransferase activity. Based on these results we propose a model whereby lipidation targets Wnt-1 to secretory vesicles that deliver the ligand to specialized microdomains at the cell surface where it can be packaged for secretion.
Received for publication, March 26, 2004 , and in revised form, May 26, 2004.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Present address: Dept. of Pharmacology, Loyola University Medical Center, 2160 S. 1st Ave., Maywood, IL 60153.
To whom correspondence should be addressed. Tel.: 413-545-4031; Fax: 413-577-4031; E-mail: susanc{at}biochem.umass.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Ching, H. C. Hang, and R. Nusse Lipid-independent Secretion of a Drosophila Wnt Protein J. Biol. Chem., June 20, 2008; 283(25): 17092 - 17098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hebbar, E. Lee, M. Manna, S. Steinert, G. S. Kumar, M. Wenk, T. Wohland, and R. Kraut A fluorescent sphingolipid binding domain peptide probe interacts with sphingolipids and cholesterol-dependent raft domains J. Lipid Res., May 1, 2008; 49(5): 1077 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Galli, T. L. Barnes, S. S. Secrest, T. Kadowaki, and L. W. Burrus Porcupine-mediated lipid-modification regulates the activity and distribution of Wnt proteins in the chick neural tube Development, September 15, 2007; 134(18): 3339 - 3348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Komekado, H. Yamamoto, T. Chiba, and A. Kikuchi Glycosylation and palmitoylation of Wnt-3a are coupled to produce an active form of Wnt-3a Genes Cells, April 1, 2007; 12(4): 521 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Coudreuse and H. C. Korswagen The making of Wnt: new insights into Wnt maturation, sorting and secretion Development, January 1, 2007; 134(1): 3 - 12. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Goodman, S. Thombre, Z. Firtina, D. Gray, D. Betts, J. Roebuck, E. P. Spana, and E. M. Selva Sprinter: a novel transmembrane protein required for Wg secretion and signaling Development, December 15, 2006; 133(24): 4901 - 4911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Resh Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules Sci. Signal., October 31, 2006; 2006(359): re14 - re14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. He and J. D. Axelrod A WNTer wonderland in Snowbird. Development, July 1, 2006; 133(14): 2597 - 2603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Mitchell, A. Vasudevan, M. E. Linder, and R. J. Deschenes Thematic review series: Lipid Posttranslational Modifications. Protein palmitoylation by a family of DHHC protein S-acyltransferases J. Lipid Res., June 1, 2006; 47(6): 1118 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Prasad and S. G. Clark Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans Development, May 1, 2006; 133(9): 1757 - 1766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. T. Struewing, A. Toborek, and C. D. Mao Mitochondrial and Nuclear Forms of Wnt13 Are Generated via Alternative Promoters, Alternative RNA Splicing, and Alternative Translation Start Sites J. Biol. Chem., March 17, 2006; 281(11): 7282 - 7293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Marois, A. Mahmoud, and S. Eaton The endocytic pathway and formation of the Wingless morphogen gradient Development, January 15, 2006; 133(2): 307 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Avisar, M. Segal, B. Sneh, and A. Zilberstein Cell-cycle-dependent resistance to Bacillus thuringiensis Cry1C toxin in Sf9 cells J. Cell Sci., July 15, 2005; 118(14): 3163 - 3171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Xin, R. E. Mains, and B. A. Eipper Monooxygenase X, a Member of the Copper-dependent Monooxygenase Family Localized to the Endoplasmic Reticulum J. Biol. Chem., November 12, 2004; 279(46): 48159 - 48167. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
