- THIS ARTICLE
- Full Text (Rapid PDF)
-
All Versions of this Article:
genetics.106.061853v1
174/1/331 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Waldrop, S.
- Articles by Wharton, Jr., K. A
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Waldrop, S.
- Articles by Wharton, Jr., K. A
doi:10.1534/genetics.106.061853
A more recent version of this article appeared on September 1, 2006.
REGULAR RESEARCH PAPERS |
An unconventional nuclear localization motif is crucial for function of the Drosophila Wnt/Wingless antagonist Naked cuticle
Sharon Waldrop 1, Chih-Chiang Chan 1, Tolga Cagatay 1, Shu Zhang 1, Raphael Rousset 2, Judy Mack 2, Wenlin Zeng 2, Matt Fish 2, Mei Zhang 1, Manami Amanai 1 and Keith A Wharton, Jr. 1*
1 UT Southwestern
2 Stanford
* To whom correspondence should be addressed. E-mail: keith.wharton{at}utsouthwestern.edu.
Submitted on June 11, 2006
Revised on July 10, 2006
Accepted on 13 July 2006
Wnt/
-catenin signals orchestrate cell fate and behavior throughout the animal kingdom. Aberrant Wnt signaling impacts nearly the entire spectrum of human disease, including birth defects, cancer, and osteoporosis. If Wnt signaling is to be effectively manipulated for therapeutic advantage, we must first understand how Wnt signals are normally controlled. Naked cuticle (Nkd) is a novel and evolutionarily conserved inducible antagonist of Wnt/-catenin signaling that is crucial for segmentation in the model genetic organism, the fruit fly Drosophila melanogaster. Nkd can bind and inhibit the Wnt signal transducer Dishevelled (Dsh), but the mechanism by which Nkd limits Wnt signaling in the fly embryo is not understood. Here we show that nkd mutants exhibit elevated levels of the -catenin homolog Armadillo but no alteration in Dsh abundance or distribution. In the fly embryo, Nkd and Dsh are predominantly cytoplasmic, though a recent report suggests that vertebrate Dsh requires nuclear localization for activity in gain-of-function assays. While Dsh-binding regions of Nkd contribute to its activity, we identify a conserved 30 amino acid motif, separable from Dsh-binding regions, that is essential for Nkd function and nuclear localization. Replacement of the 30 aa motif with a conventional nuclear localization sequence rescued a small fraction of nkd mutant animals to adulthood. Our studies suggest that Nkd targets Dsh-dependent signal transduction steps in both cytoplasmic and nuclear compartments of cells receiving the Wnt signal.
Key Words: Dishevelled, Drosophila, Naked cuticle, Wingless, Wnt
This article has been cited by other articles:
 |
|
 |
|
  W. Wu, R. F. Xu, L. Xiao, H. Xu, and G. Gao Expression of the -Catenin Gene in the Skin of Embryonic Geese During Feather Bud Development Poult. Sci., January 1, 2008; 87(1): 204 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhang, T. Cagatay, M. Amanai, M. Zhang, J. Kline, D. H. Castrillon, R. Ashfaq, O. K. Oz, and K. A. Wharton Jr. Viable Mice with Compound Mutations in the Wnt/Dvl Pathway Antagonists nkd1 and nkd2 Mol. Cell. Biol., June 15, 2007; 27(12): 4454 - 4464. [Abstract] [Full Text] [PDF]
|
|