A molecular mechanism for Wnt ligand-specific signaling

Author:

Eubelen Marie1ORCID,Bostaille Naguissa1ORCID,Cabochette Pauline1,Gauquier Anne1,Tebabi Patricia1,Dumitru Andra C.2,Koehler Melanie2ORCID,Gut Philipp1,Alsteens David2ORCID,Stainier Didier Y. R.3ORCID,Garcia-Pino Abel45ORCID,Vanhollebeke Benoit156ORCID

Affiliation:

1. Laboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles (ULB), Gosselies B-6041, Belgium.

2. NanoBiophysics Laboratory, Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium.

3. Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.

4. Laboratory of Cellular and Molecular Microbiology, Department of Molecular Biology, ULB, Gosselies B-6041, Belgium.

5. Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Belgium.

6. Center for Microscopy and Molecular Imaging (CMMI), ULB, Gosselies B-6041, Belgium.

Abstract

How Wnt ligands achieve specificity Wnt signaling is essential for development, tissue homeostasis, and disease. The 19 members of the Wnt family interact promiscuously with the 10 Frizzled receptors, raising the question of how ligand-specific discrimination is achieved in a biological context. Eubelen et al. used experiments in zebrafish to show that cells are equipped with decoding modules that bind Wnt with high specificity and trigger signal amplification via their recruitment into higher-order Frizzled signalosomes (see the Perspective by Kim and Goentoro). Thus, distinct Wnt ligand-receptor pairs can be targeted specifically for therapeutic purposes. Science , this issue p. eaat1178 ; see also p. 643

Funder

Fonds De La Recherche Scientifique - FNRS

European Regional Development Fund

FRFS-Welbio

Queen Elisabeth Medical Foundation for Neurosciences

Fondation Université libre de Bruxelles

Concerted Research Action

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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