期刊
FEBS JOURNAL
卷 284, 期 15, 页码 2513-2526出版社
WILEY
DOI: 10.1111/febs.14139
关键词
canonical Wnt; lipid raft; plasma membrane lipid; membrane trafficking; Wnt/beta-catenin pathway
资金
- EMBO
- Marie Sklodowska-Curie Intra-European (MEMBRANE DYNAMICS)
- National University of Singapore
- Ministry of Education of Singapore [MOE2014-T2-2-115, R-154-000-663-112]
- Scientific and Technological Research Council of Turkey (TUBITAK [114Z192]
- Newton-Katip Celebi Fund
- Wolfson Foundation
- Medical Research Council (MRC) [MC_UU_12010/unit, G0902418, MC_UU_12025]
- MRC/BBSRC/EPSRC [MR/K01577X/1]
- Wellcome Trust [104924/14/Z/14]
- MRC [MR/K01577X/1, G0902418, MC_UU_00008/9, MC_UU_12010/9] Funding Source: UKRI
- Medical Research Council [MR/K01577X/1, G0902418, MC_UU_00008/9, MC_UU_12010/9] Funding Source: researchfish
- Wellcome Trust [107457/Z/15/Z] Funding Source: researchfish
While the cytosolic events of Wnt/beta-catenin signaling (canonical Wnt signaling) pathway have been widely studied, only little is known about the molecular mechanisms involved in Wnt binding to its receptors at the plasma membrane. Here, we reveal the influence of the immediate plasma membrane environment on the canonical Wnt-receptor interaction. While the receptors are distributed both in ordered and disordered environments, Wnt binding to its receptors selectively occurs in more ordered membrane environments which appear to cointernalize with the Wnt-receptor complex. Moreover, Wnt/b-catenin signaling is significantly reduced when the membrane order is disturbed by specific inhibitors of certain lipids that prefer to localize at the ordered environments. Similarly, a reduction in Wnt signaling activity is observed in Niemann-Pick Type C disease cells where trafficking of ordered membrane lipid components to the plasma membrane is genetically impaired. We thus conclude that ordered plasma membrane environments are essential for binding of canonical Wnts to their receptor complexes and downstream signaling activity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据