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Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis

Rothbächer, Ute and Laurent, Micheline N. and Deardorff, Matthew A. and Klein, Peter S. and Cho, Ken W. Y. and Fraser, Scott E. (2000) Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. EMBO Journal, 19 (5). pp. 1010-1022. ISSN 0261-4189. https://resolver.caltech.edu/CaltechAUTHORS:20160216-082212925

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Abstract

Dishevelled (Dsh) induces a secondary axis and can translocate to the membrane when activated by Frizzleds; however, dominant-negative approaches have not supported a role for Dsh in primary axis formation. We demonstrate that the Dsh protein is post-translationally modified at the dorsal side of the embryo: timing and position of this regulation suggests a role of Dsh in dorsal–ventral patterning in Xenopus. To create functional links between these properties of Dsh we analyzed the influence of endogenous Frizzleds and the Dsh domain dependency for these characteristics. Xenopus Frizzleds phosphorylate and translocate Xdsh to the membrane irrespective of their differential ectopic axes inducing abilities, showing that translocation is insufficient for axis induction. Dsh deletion analysis revealed that axis inducing abilities did not segregate with Xdsh membrane association. The DIX region and a short stretch at the N-terminus of the DEP domain are necessary for axis induction while the DEP region is required for Dsh membrane association and its phosphorylation. In addition, Dsh forms homomeric complexes in embryos suggesting that multimerization is important for its proper function.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1093/emboj/19.5.1010DOIArticle
http://onlinelibrary.wiley.com/doi/10.1093/emboj/19.5.1010/abstractPublisherArticle
ORCID:
AuthorORCID
Fraser, Scott E.0000-0002-5377-0223
Additional Information:© 2000 European Molecular Biology Organization. Received July 14, 1999; revised and accepted December 21, 1999. Article first published online: 1 Mar 2000. We thank R. Nusse for anti-Ddsh and anti-Dvl-1 antibodies and discussion prior to publication, R. Moon for pCS2-rat frizzled-1 and -2 constructs and for anti-β-catenin antiserum, I.L. Blitz for HA epitope oligos and for helpful discussion and friendship throughout the course of this work, S. Sokol for myc-Xdsh, C. LaBonne and R. Davis for the CS2P–GFP construct, J. Axelrod and M. Mlodzik for communication of results prior to publication, C. Marcelle, C. LaBonne, I.L. Blitz, A. Knecht and M. Dickinson for initial comments on the manuscript, and Jacques Pradel and Patrick Lemaire for support. This work was supported by grants from Boehringer Ingelheim Fonds (to U.R.), NIH HD29507 and Pew Scholars Program in Biomedical Sciences (to K.W.Y.C.) and NIMH MH49176, HD25390 and DA/MH08944-05 (to S.E.F.). K.W.Y. Cho and S.E. Fraser contributed equally to this work.
Funders:
Funding AgencyGrant Number
Boehringer Ingelheim FondsUNSPECIFIED
NIHHD29507
Pew Scholars Program in Biomedical SciencesUNSPECIFIED
National Institute of Mental Health (NIMH)MH49176
National Institute of Mental Health (NIMH)HD25390
National Institute of Mental Health (NIMH)DA/MH08944-05
Subject Keywords:axis formation; DEP; Dishevelled; Frizzled; Wnt signaling
Issue or Number:5
Record Number:CaltechAUTHORS:20160216-082212925
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160216-082212925
Official Citation:Rothbächer, U., Laurent, M. N., Deardorff, M. A., Klein, P. S., Cho, K. W.Y. and Fraser, S. E. (2000), Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. The EMBO Journal, 19: 1010–1022. doi: 10.1093/emboj/19.5.1010
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64488
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:17 Feb 2016 21:50
Last Modified:03 Oct 2019 09:38

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