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

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Autorinnen und Autoren: Bryja V, Andersson ER, Schambony A, Esner M, Bryjova L, Biris KK, Hall AC, Kraft B, Cajanek L, Yamaguchi TP, Buckingham M, Arenas E
Zeitschrift: Molecular Biology of the Cell
Jahr der Veröffentlichung: 2009
Band: 20
Heftnummer: 3
Seitenbereich: 924-936
ISSN: 1059-1524


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.

FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Schambony, Alexandra Prof. Dr.
Lehrstuhl für Entwicklungsbiologie

Einrichtungen weiterer Autorinnen und Autoren

Institut Pasteur
Karlsruhe Institute of Technology (KIT)
Karolinska Institute
National Cancer Institute (NCI)


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.

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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