A secreted splice variant of the Xenopus frizzled-4 receptor is a biphasic modulator of Wnt signalling

Cell Communication and Signaling

Short Report

Herbert Steinbeisser¹  Lilian T Kaufmann¹  Anne-Kathrin Gorny¹  Rajeeb K Swain² 

[1] Section Developmental Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, D-69120, Heidelberg, Germany;Vascular Biology Laboratory, Institute of Life Sciences, Nalco Square, 751023, Bhubaneswar, India;

关键词: Fz4-v1;    Splice variant frizzled-4 receptor;    Biphasic;    Wnt signalling;    SFRP;    Xenopus;    Dorsal fin;    Neural crest;   

DOI  :  10.1186/1478-811X-11-89

 received in 2013-03-27, accepted in 2013-11-11,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundActivation of the Wnt signalling cascade is primarily based on the interplay between Wnt ligands, their receptors and extracellular modulators. One prominent family of extracellular modulators is represented by the SFRP (secreted Frizzled-related protein) family. These proteins have significant similarity to the extracellular domain of Frizzled receptors, suggesting that they bind Wnt ligands and inhibit signalling. The SFRP-type protein Fz4-v1, a splice variant of the Frizzled-4 receptor found in humans and Xenopus, was shown to augment Wnt/β-catenin signalling, and also interacts with those Wnt ligands that act on β-catenin-independent Wnt pathways.FindingsHere we show that Xenopus Fz4-v1 can activate and inhibit the β-catenin-dependent Wnt pathway. Gain-of-function experiments revealed that high Wnt/β-catenin activity is inhibited by low and high concentrations of Fz4-v1. In contrast, signals generated by low amounts of Wnt ligands were enhanced by low concentrations of Fz4-v1 but were repressed by high concentrations. This biphasic activity of Fz4-v1 was not observed in non-canonical Wnt signalling. Fz4-v1 enhanced β-catenin-independent Wnt signalling triggered by either low or high doses of Wnt11. Antisense morpholino-mediated knock-down experiments demonstrated that in early Xenopus embryos Fz4-v1 is required for the migration of cranial neural crest cells and for the development of the dorsal fin.ConclusionsFor the first time, we show that a splice variant of the Frizzled-4 receptor modulates Wnt signalling in a dose-dependent, biphasic manner. These results also demonstrate that the cystein-rich domain (CRD), which is shared by Fz4-v1 and SFRPs, is sufficient for the biphasic activity of these secreted Wnt modulators.

【 授权许可】

Unknown   
© Gorny et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.