E-cadherin dis-engagement activates the Rap1 GTPase.

E-cadherin dis-engagement activates the Rap1 GTPase.
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E-钙黏着蛋白的分离激活RAP1 GTPase。

DOI:
10.1002/jcb.21902
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发表时间:
2008-11-01
影响因子:
4
通讯作者:
Quilliam, Lawrence A.
Quilliam, Lawrence A.
中科院分区:
生物学2区
文献类型:
--
作者:
Asuri, Sirisha;Yan, Jingliang;Paranavitana, Nivanka C.;Quilliam, Lawrence A.

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基于E-钙粘蛋白的粘附连接被多种细胞信号传导事件精细调节。在这里,我们表明,Ras相关的Rap 1 GTdR是丰富的新生细胞与细胞接触的区域,并加强E-钙粘蛋白连接:组成型活性Rap 1表达MDCK细胞表现出增加的连接接触和抵抗钙耗竭诱导的细胞与细胞连接破坏。E-cadherin脱离激活Rap 1,这与E-cadherin与Rap GEFs、C3 G和PDZ-GEFI的相关性相关。PDZ-GEF I与E-钙粘蛋白和β-连环蛋白相关,而C3 G与E-钙粘蛋白的相互作用不涉及β-连环蛋白。MDCK细胞中PDZ-GEF I的敲低降低了E-钙粘蛋白连接破坏后Rap 1的活性。我们在此证明Rap 1在E-cadherin连接的维持和修复中起作用,并通过由E-cadherin启动的“由外向内”信号通路激活,至少部分由PDZ-GEF I介导。
E-cadherin based adherens junctions are finely regulated by multiple cellular signaling events. Here we show that the Ras-related Rap1 GTPase is enriched in regions of nascent cell-cell contacts and strengthens E-cadherin junctions: constitutively active Rap1 expressing MDCK cells exhibit increased junctional contact and resisted calcium depletion-induced cell-cell junction disruption. E-cadherin disengagement activated Rap1 and this correlated with E-cadherin association with the Rap GEFs, C3G and PDZ-GEF I. PDZ-GEF I associated with E-cadherin and β-catenin whereas C3G interaction with E-cadherin did not involve β-catenin. Knockdown of PDZ-GEF I in MDCK cells decreased Rap1 activity following E-cadherin junction disruption. We hereby show that Rap1 plays a role in the maintenance and repair of E-cadherin junctions and is activated via an “outside-in” signaling pathway initiated by E-cadherin and mediated at least in part by PDZ-GEF I.
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