Research article summary (published 16 Jul 2006):

An unconventional nuclear localization motif is crucial for function of the Drosophila Wnt/wingless antagonist Naked cuticle.

Full Abstract

Wnt/beta-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 first must understand how Wnt signals are normally controlled. Naked cuticle (Nkd) is a novel and evolutionarily conserved inducible antagonist of Wnt/beta-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 beta-catenin homolog Armadillo but no alteration in Dsh abundance or distribution. In the fly embryo, Nkd and Dsh are predominantly cytoplasmic, although 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.

Author information

Author/s: Waldrop, Sharon (S); Chan, Chih-Chiang (CC); Cagatay, Tolga (T); Zhang, Shu (S); Rousset, Raphaël (R); Mack, Judy (J); Zeng, Wenlin (W); Fish, Matt (M); Zhang, Mei (M); Amanai, Manami (M); Wharton, Keith A (KA);

Affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9072, USA.

Grants: K08 HD001164-03 (Agency:NICHD NIH HHS) ; K08 HD001164-04 (Agency:NICHD NIH HHS) ; K08 HD001164-05 (Agency:NICHD NIH HHS) ; K08 HD001164-06 (Agency:NICHD NIH HHS) ; K08-HD01164 (Agency:NICHD NIH HHS) ; R01 GM065404-01A1 (Agency:NIGMS NIH HHS) ; R01 GM065404-02 (Agency:NIGMS NIH HHS) ; R01 GM065404-03 (Agency:NIGMS NIH HHS) ; R01 GM065404-04 (Agency:NIGMS NIH HHS) ; R01-GM65404 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Genetics (Genetics), published in United States. (Language: eng)

Reference: 2006-Sep; vol 174 (issue 1) : pp 331-48

Dates: Created 2006/09/21; Completed 2006/12/18; Revised 2008/11/21;

PMID: 16849595, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Active Transport, Cell Nucleus - physiology Adaptor Proteins, Signal Transducing - chemistry; metabolism Amino Acid Motifs - physiology Amino Acid Sequence Animals Anopheles gambiae - genetics Armadillo Domain Proteins - metabolism Cytoplasm - metabolism Drosophila - embryology; genetics; metabolism Drosophila Proteins - antagonists & inhibitors; chemistry; genetics; metabolism; physiology Embryo, Nonmammalian Mice Models, Biological Molecular Sequence Data

Molecular Sequence Data Mutant Proteins - physiology Mutation Nuclear Localization Signals - physiology Phosphoproteins - chemistry; metabolism Protein Binding Proto-Oncogene Proteins - antagonists & inhibitors; metabolism Sequence Homology, Amino Acid Signal Transduction Tissue Distribution Transcription Factors - metabolism Wnt Proteins - antagonists & inhibitors; metabolism Wnt1 Protein beta Catenin - metabolism

Associated Chemicals: Adaptor Proteins, Signal Transducing (0) ; Armadillo Domain Proteins (0) ; Drosophila Proteins (0) ; Mutant Proteins (0) ; Nuclear Localization Signals (0) ; Phosphoproteins (0) ; Proto-Oncogene Proteins (0) ; Transcription Factors (0) ; Wnt Proteins (0) ; Wnt1 Protein (0) ; armadillo protein, Drosophila (0) ; beta Catenin (0) ; dishevelled proteins (0) ; naked cuticle protein, Drosophila (0) ; wg protein, Drosophila (0)

Related articles

These are the highest related articles currently in the database:

• CKIepsilon/discs overgrown promotes both Wnt-Fz/beta-catenin and Fz/PCP signaling in Drosophila. 9 Jul 2006
• Notch synergizes with axin to regulate the activity of armadillo in Drosophila. 29 Sep 2006
• Dual positive and negative regulation of wingless signaling by adenomatous polyposis coli. 16 Jan 2008
• Wingless-independent association of Pygopus with dTCF target genes. 20 Feb 2007
• Novel TCF-binding sites specify transcriptional repression by Wnt signalling. 15 Apr 2008
• BCL9-2 binds Arm/beta-catenin in a Tyr142-independent manner and requires Pygopus for its function in Wg/Wnt signaling. 28 Sep 2006
• Analysis of combinatorial effects of Wnts and Frizzleds on beta-catenin/armadillo stabilization and Dishevelled phosphorylation. 30 Aug 2005
• Characterization of the Drosophila myeloid leukemia factor. 29 Nov 2006
• Drosophila Naked cuticle (Nkd) engages the nuclear import adaptor Importin-alpha3 to antagonize Wnt/beta-catenin signaling. 16 Mar 2008
• Components of wingless signalling in Drosophila. 4 Jan 1994

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.