GTC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Genes to Cells (2007) 12, 521-534. doi:10.1111/j.1365-2443.2007.01068.x
© 2007 Blackwell Publishing or its licensors
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Komekado, H.
Right arrow Articles by Kikuchi, A.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Komekado, H.
Right arrow Articles by Kikuchi, A.

Glycosylation and palmitoylation of Wnt-3a are coupled to produce an active form of Wnt-3a

 Hideyuki Komekado1,2, Hideki Yamamoto1, Tsutomu Chiba2 and Akira Kikuchi1,*

1 Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
2 Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

Wnt-3a is a representative ligand that activates the ß-catenin-dependent pathway in Wnt signaling and is modified with glycans and palmitate. In this study, we analyzed the relationship between glycosylation and lipidation of Wnt-3a. Secretion of a Wnt-3a mutant that lacks glycosylation (Wnt-3a NQ) was impaired. Wnt-3a C77A, which lacks palmitoylation at Cys77, was secreted with similar efficiency to wild-type Wnt-3a (Wnt-3a WT), but did not induce the internalization of low-density lipoprotein receptor-related protein 6 (LRP6). Furthermore, removal of palmitate from Wnt-3a suppressed the ability to bind to its receptors Frizzled8 and LRP6. Wnt-3a C77A was glycosylated to an extent similar to Wnt-3a WT, while Wnt-3a NQ was not modified with palmitate. Expression of porcupine, which is a putative acyltransferase, enhanced palmitoylation of Wnt-3a WT greatly, but that of Wnt-3a NQ slightly. While Wnt-3a WT was present in both the endoplasmic reticulum (ER) and Golgi, Wnt-3a NQ was located to the ER only. Furthermore, Wnt-3a was not palmitoylated but was glycosylated in the cells treated with Brefeldin A, which inhibits transport of vesicles from the ER to the Golgi. These results indicate that glycosylation of Wnt-3a precedes palmitoylation and that both modifications are necessary for secretion of an active Wnt-3a.

Communicated by: Kozo Kaibuchi

* Correspondence: E-mail: akikuchi{at}hiroshima-u.ac.jp




This article has been cited by other articles:


Home page
 Cold Spring Harb. Perspect. Biol.Home page
K. M. Cadigan and M. Peifer
Wnt signaling from development to disease: insights from model systems.
Cold Spring Harb Perspect Biol, August 1, 2009; 1(2): a002881 - a002881.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb Symp Quant BiolHome page
R. Nusse, C. Fuerer, W. Ching, K. Harnish, C. Logan, A. Zeng, D. ten Berge, and Y. Kalani
Wnt Signaling and Stem Cell Control
Cold Spring Harb Symp Quant Biol, November 26, 2008; (2008) sqb.2008.73.035v2.
[Abstract] [PDF]

Home page
 J. Biol. Chem.Home page
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]

Home page
 DevelopmentHome page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS
Copyright © 2007 by Wiley-Blackwell Publishing.