The frizzled extracellular domain is a ligand for Van Gogh/Stbm during nonautonomous planar cell polarity signaling.

The frizzled extracellular domain is a ligand for Van Gogh/Stbm during nonautonomous planar cell polarity signaling.
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DOI:
10.1016/j.devcel.2008.08.004
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发表时间:
2008-09
期刊:
影响因子:
11.8
通讯作者:
Mlodzik, Marek
Mlodzik, Marek
中科院分区:
生物学1区
文献类型:
--
作者:
Wu, Jun;Mlodzik, Marek

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卷曲(Fz)受体是Wnt/β-连环蛋白和平面细胞极性(PCP)信号传导的细胞自主需要。除了这些要求外,Fz在PCP建立过程中非自主地起作用:Fz -斑块周围的野生型细胞重新定向到Fz -细胞。非自主Fz信号的分子机制尚不清楚。我们的体内研究确定了Fz的细胞外结构域(ECD),特别是其富含半胱氨酸的结构域(CRD),对于非自主Fz- pcp活性至关重要。重要的是,我们证明了FzECD和跨膜蛋白Van Gogh/Strabismus (Vang/Stbm)之间的生化和物理相互作用。我们发现这种功能先于细胞自主相互作用和可见的不对称PCP因子定位。我们的数据表明,Vang/Stbm可以作为FzECD受体,允许细胞感知其邻居的Fz活性/水平。因此,Fz-Vang/Stbm的直接相互作用代表了一种有趣的机制,可以解释细胞在上皮场平面内的全局定向。
The Frizzled (Fz) receptor is required cell autonomously in Wnt/β-catenin and planar cell polarity (PCP) signaling. In addition to these requirements, Fz acts nonautonomously during PCP establishment: wild-type cells surrounding fz− patches reorient toward the fz− cells. The molecular mechanism(s) of nonautonomous Fz signaling are unknown. Our in vivo studies identify the extracellular domain (ECD) of Fz, in particular its CRD (cysteine rich domain), as critical for nonautonomous Fz-PCP activity. Importantly, we demonstrate biochemical and physical interactions between the FzECD and the transmembrane protein Van Gogh/Strabismus (Vang/Stbm). We show that this function precedes cell-autonomous interactions and visible asymmetric PCP factor localization. Our data suggest that Vang/Stbm can act as a FzECD receptor, allowing cells to sense Fz activity/levels of their neighbors. Thus, direct Fz-Vang/Stbm interactions represent an intriguing mechanism that may account for the global orientation of cells within the plane of their epithelial field.
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