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

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Tauriello DVF, Jordens I, Kirchner K, Slootstra JW, Kruitwagen T, Bouwman BAM, Noutsou M, Rudiger SGD, Schwamborn K, Schambony A, Maurice MM
Zeitschrift: Proceedings of the National Academy of Sciences of the United States of America
Jahr der Veröffentlichung: 2012
Band: 109
Heftnummer: 14
Seitenbereich: E812-20
ISSN: 0027-8424
eISSN: 1091-6490


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.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Kirchner, Katharina
Lehrstuhl für Entwicklungsbiologie
Schambony, Alexandra Prof. Dr.
Lehrstuhl für Entwicklungsbiologie


Einrichtungen weiterer Autorinnen und Autoren

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


Zitierweisen

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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