Wnt-11 and Fz7 reduce cell adhesion in convergent extension by sequestration of PAPC and C-cadherin.

Wnt-11 and Fz7 reduce cell adhesion in convergent extension by sequestration of PAPC and C-cadherin.
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DOI:
10.1083/jcb.201110076
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发表时间:
2012-08-20
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Wedlich D
Wedlich D
中科院分区:
其他
文献类型:
--
作者:
Kraft B;Berger CD;Wallkamm V;Steinbeisser H;Wedlich D

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Wnt-11/ zzzzed -7通过捕获原钙粘蛋白PAPC和c -钙粘蛋白形成不同的粘附调节复合物,减少c -钙粘蛋白的横向聚集。在非洲爪蟾原肠胚形成过程中,Wnt-11/平面细胞极性信号通路使正在进行会聚伸展的中胚层细胞极化。这些与侧插行为相关的形状变化需要细胞粘附的动态调节。在本文中,我们报道了Wnt-11/ zzzzled -7 (Fz7)通过不同的Fz7相互作用域与旁轴原钙粘蛋白(PAPC,表示为AMCP)和c -钙粘蛋白(表示为AMCC)形成单独的粘附调节复合物(AMCs)来控制细胞粘附。当PAPC是Wnt-11-Fz7复合体的一部分时,其依赖于Dynamin1和网格蛋白的内化被阻断。Wnt-11对AMCP (Fz7/PAPC)的膜稳定性阻止了C-cadherin聚集,导致细胞粘附降低和细胞分选活性改变。重要的是,Wnt-11不影响c -钙粘蛋白内化;相反,它促进AMCC (Fz7/Cadherin)的形成,与C-cadherin的顺式二聚化相竞争。由于PAPC和C-cadherin不直接相互作用,也不与Fz7形成联合复合体,我们认为Wnt-11触发两种不同复合体AMCC和AMCP的形成,这两种复合体通过阻碍C-cadherin的横向聚集而平行作用,以减少细胞粘附。
Wnt-11/frizzled-7 reduces the lateral clustering of C-cadherin by capturing the protocadherin PAPC and C-cadherin into distinct adhesion-modulating complexes. Wnt-11/planar cell polarity signaling polarizes mesodermal cells undergoing convergent extension during Xenopus laevis gastrulation. These shape changes associated with lateral intercalation behavior require a dynamic modulation of cell adhesion. In this paper, we report that Wnt-11/frizzled-7 (Fz7) controls cell adhesion by forming separate adhesion-modulating complexes (AMCs) with the paraxial protocadherin (PAPC; denoted as AMCP) and C-cadherin (denoted as AMCC) via distinct Fz7 interaction domains. When PAPC was part of a Wnt-11–Fz7 complex, its Dynamin1- and clathrin-dependent internalization was blocked. This membrane stabilization of AMCP (Fz7/PAPC) by Wnt-11 prevented C-cadherin clustering, resulting in reduced cell adhesion and modified cell sorting activity. Importantly, Wnt-11 did not influence C-cadherin internalization; instead, it promoted the formation of AMCC (Fz7/Cadherin), which competed with cis-dimerization of C-cadherin. Because PAPC and C-cadherin did not directly interact and did not form a joint complex with Fz7, we suggest that Wnt-11 triggers the formation of two distinct complexes, AMCC and AMCP, that act in parallel to reduce cell adhesion by hampering lateral clustering of C-cadherin.
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