The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo.

Bryja V, Andersson ER, Schambony A, Esner M, Bryjova L, Biris KK, Hall AC, Kraft B, Cajanek L, Yamaguchi TP, Buckingham M, Arenas E (2009)

Publication Type: Journal article, Original article

Subtype: other

Publication year: 2009

Journal

Molecular Biology of the Cell American Society for Cell Biology

Book Volume: 20

Pages Range: 924-936

Journal Issue: 3

URI: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=19056682&retmode=ref&cmd=prlinks

DOI: 10.1091/mbc.E08-07-0711

Abstract

Lrp5/6 are crucial coreceptors for Wnt/beta-catenin signaling, a pathway biochemically distinct from noncanonical Wnt signaling pathways. Here, we examined the possible participation of Lrp5/6 in noncanonical Wnt signaling. We found that Lrp6 physically interacts with Wnt5a, but that this does not lead to phosphorylation of Lrp6 or activation of the Wnt/beta-catenin pathway. Overexpression of Lrp6 blocks activation of the Wnt5a downstream target Rac1, and this effect is dependent on intact Lrp6 extracellular domains. These results suggested that the extracellular domain of Lrp6 inhibits noncanonical Wnt signaling in vitro. In vivo, Lrp6-/- mice exhibited exencephaly and a heart phenotype. Surprisingly, these defects were rescued by deletion of Wnt5a, indicating that the phenotypes resulted from noncanonical Wnt gain-of-function. Similarly, Lrp5 and Lrp6 antisense morpholino-treated Xenopus embryos exhibited convergent extension and heart phenotypes that were rescued by knockdown of noncanonical XWnt5a and XWnt11. Thus, we provide evidence that the extracellular domains of Lrp5/6 behave as physiologically relevant inhibitors of noncanonical Wnt signaling during Xenopus and mouse development in vivo.

Authors with CRIS profile

Alexandra Schambony Lehrstuhl für Entwicklungsbiologie

Involved external institutions

Karolinska Institute SE Sweden (SE) Institut Pasteur FR France (FR) National Cancer Institute (NCI) US United States (USA) (US) Karlsruhe Institute of Technology (KIT) DE Germany (DE)

How to cite

APA:

Bryja, V., Andersson, E.R., Schambony, A., Esner, M., Bryjova, L., Biris, K.K.,... Arenas, E. (2009). The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo. Molecular Biology of the Cell, 20(3), 924-936. https://dx.doi.org/10.1091/mbc.E08-07-0711

MLA:

Bryja, Vitezslav, et al. "The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo." Molecular Biology of the Cell 20.3 (2009): 924-936.

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