Functional role of the Frizzled linker domain in the Wnt signaling pathway.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
05 05 2022
05 05 2022
Historique:
received:
14
06
2021
accepted:
14
04
2022
entrez:
5
5
2022
pubmed:
6
5
2022
medline:
10
5
2022
Statut:
epublish
Résumé
The Wnt signaling pathway plays a critical role in the developmental and physiological processes of metazoans. We previously reported that the Frizzled4 (FZD4) linker domain plays an important role in Norrin binding and signaling. However, the question remains whether the FZD linker contributes to Wnt signaling in general. Here, we show that the FZD linker is involved in Wnt binding and affects downstream Wnt signaling. A FZD4 chimera, in which the linker was swapped with that of the non-canonical receptor FZD6, impairs the binding with WNT3A and suppresses the recruitment of LRP6 and Disheveled, resulting in reduced canonical signaling. A similar effect was observed for non-canonical signaling. A FZD6 chimera containing the FZD1 linker showed reduced WNT5A binding and impaired signaling in ERK, JNK, and AKT mediated pathways. Altogether, our results suggest that the FZD linker plays an important role in specific Wnt binding and intracellular Wnt signaling.
Identifiants
pubmed: 35513706
doi: 10.1038/s42003-022-03370-4
pii: 10.1038/s42003-022-03370-4
pmc: PMC9072438
doi:
Substances chimiques
Carrier Proteins
0
Frizzled Receptors
0
Wnt Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
421Informations de copyright
© 2022. The Author(s).
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