Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled.

Tauriello DVF, Jordens I, Kirchner K, Slootstra JW, Kruitwagen T, Bouwman BAM, Noutsou M, Rudiger SGD, Schwamborn K, Schambony A, Maurice MM (2012)

Publication Type: Journal article, Original article

Subtype: other

Publication year: 2012

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 109

Pages Range: E812-20

Journal Issue: 14

URI: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=22411803&retmode=ref&cmd=prlinks

DOI: 10.1073/pnas.1114802109

Abstract

Wnt binding to members of the seven-span transmembrane Frizzled (Fz) receptor family controls essential cell fate decisions and tissue polarity during development and in adulthood. The Fz-mediated membrane recruitment of the cytoplasmic effector Dishevelled (Dvl) is a critical step in Wnt/β-catenin signaling initiation, but how Fz and Dvl act together to drive downstream signaling events remains largely undefined. Here, we use an Fz peptide-based microarray to uncover a mechanistically important role of the bipartite Dvl DEP domain and C terminal region (DEP-C) in binding a three-segmented discontinuous motif in Fz. We show that cooperative use of two conserved motifs in the third intracellular loop and the classic C-terminal motif of Fz is required for DEP-C binding and Wnt-induced β-catenin activation in cultured cells and Xenopus embryos. Within the complex, the Dvl DEP domain mainly binds the Fz C-terminal tail, whereas a short region at the Dvl C-terminal end is required to bind the Fz third loop and stabilize the Fz-Dvl interaction. We conclude that Dvl DEP-C binding to Fz is a key event in Wnt-mediated signaling relay to β-catenin. The discontinuous nature of the Fz-Dvl interface may allow for precise regulation of the interaction in the control of Wnt-dependent cellular responses.

Authors with CRIS profile

Katharina Kirchner Lehrstuhl für Entwicklungsbiologie Alexandra Schambony Lehrstuhl für Entwicklungsbiologie

Involved external institutions

University Medical Centre Utrecht (UMC Utrecht) NL Netherlands (NL) Pepscan Holding NV NL Netherlands (NL) Universiteit Utrecht (UU) / Utrecht University NL Netherlands (NL)

How to cite

APA:

Tauriello, D.V.F., Jordens, I., Kirchner, K., Slootstra, J.W., Kruitwagen, T., Bouwman, B.A.M.,... Maurice, M.M. (2012). Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled. Proceedings of the National Academy of Sciences of the United States of America, 109(14), E812-20. https://dx.doi.org/10.1073/pnas.1114802109

MLA:

Tauriello, Daniele V. F., et al. "Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled." Proceedings of the National Academy of Sciences of the United States of America 109.14 (2012): E812-20.

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