Premium
Cholesterol binding is a determinant of canonical Wnt signaling activity of Dishevelled (598.3)
Author(s) -
Xin Yao
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.598.3
Subject(s) - dishevelled , wnt signaling pathway , frizzled , microbiology and biotechnology , lrp6 , lrp5 , signal transduction , biology , cell signaling , chemistry
The Wnt cell‐cell signaling pathway plays a critical and evolutionarily conserved role in directing cell fates through the β‐catenin‐dependent canonical pathway and other non‐canonical pathways like planar cell polarity (PCP) pathway. Dishevelled (Dvl) determines the direction of Wnt and PCP signaling, however, it is still unknown how Dvl directs the two pathways. Here, we show that cholesterol in the plasma membrane serves as a regulatory lipid, selectively driving the progression of canonical Wnt signaling over PCP signaling by specifically interacting with the PDZ domain of Dvl. Single Molecule imaging shows that cholesterol is essential for sustained association of Dvl with Axin in response to a canonical Wnt ligand, but not for the formation of the PCP signaling complex component like Damm1. After the treatment with the cholesterol oxidase, it shows a tremendously decrease of Dvl and Axin interaction. Single molecule tracking also shows local enrichment of cholesterol near the Frizzle receptor upon its binding to a canonical Wnt ligand through the Frizzle co‐localization with the cholesterol binding domain, D4. Collectively, our results suggest a new regulatory role of cellular cholesterol and a potential link between cellular cholesterol levels and canonical Wnt signaling activities.