WAVE regulates Cadherin junction assembly and turnover during epithelial polarization.
WAVE regulates Cadherin junction assembly and turnover during epithelial polarization.
复制标题
WAVE 在上皮极化过程中调节钙粘蛋白连接的组装和周转。
DOI：
10.1016/j.ydbio.2017.12.002
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发表时间：
2018
影响因子：
2.7
通讯作者：
Soto,MarthaC
中科院分区：
文献类型：
--
作者：
Sasidharan,Shashikala;Borinskaya,Sofya;Patel,Falshruti;Bernadskaya,Yelena;Mandalapu,Sailaja;Agapito,Maria;Soto,MarthaC
肌动蛋白是上皮顶端连接的组成部分，但分支肌动蛋白调节剂与顶端连接组件的相互作用仍然不清楚。生物化学数据表明，α-连环蛋白抑制Arp 2/3依赖的分支肌动蛋白。这些结果表明，分支肌动蛋白只需要在顶端连接发展的最早阶段。我们在开发C中使用实时成像。elegansembryos测试模型如何波诱导的分支肌动蛋白与其他顶端连接蛋白在连接的形成和成熟的基本过程。我们发现早期和晚期的重要作用，波在顶端连接的形成。早，如C。当elegansintestinal epithelium变得极化时，我们发现WAVE组分与钙粘蛋白组分同时富集，并且在DLG-1顶端积累之前。极化肠中F-肌动蛋白积累的实时成像支持钙粘蛋白复合物组分和分支肌动蛋白调节剂一起工作以富集顶端肌动蛋白。后来在交界处的发展，顶端积累的波和钙粘蛋白组件被证明是相互依赖的：钙粘蛋白复合物的损失改变波积累，和波复合物损失增加钙粘蛋白积累。为了确定为什么当WVE-1耗尽时钙粘蛋白水平升高，我们使用FRAP来分析钙粘蛋白动力学，发现WAVE以及运输蛋白EHD-1/RME-1的丢失会增加钙粘蛋白动力学。在缺乏分支肌动蛋白调节剂的成人中的EM研究支持WVE-1维持已建立的连接，推测是通过其对钙粘蛋白的运输作用。因此，我们提出了一个发展模型的连接形成分支肌动蛋白调节器紧密相连的钙粘蛋白连接，通过其以前未被重视的作用，钙粘蛋白运输。
Actin is an integral component of epithelial apical junctions, yet the interactions of branched actin regulators with apical junction components are still not clear. Biochemical data have shown that α−catenin inhibits Arp2/3-dependent branched actin. These results suggested that branched actin is only needed at earliest stages of apical junction development. We use live imaging in developingC. elegansembryos to test models for how WAVE-induced branched actin collaborates with other apical junction proteins during the essential process of junction formation and maturation. We uncover both early and late essential roles for WAVE in apical junction formation. Early, as theC. elegansintestinal epithelium becomes polarized, we find that WAVE components become enriched concurrently with the Cadherin components and before the DLG-1 apical accumulation. Live imaging of F-actin accumulation in polarizing intestine supports that the Cadherin complex components and branched actin regulators work together for apical actin enrichment. Later in junction development, the apical accumulation of WAVE and Cadherin components is shown to be interdependent: Cadherin complex loss alters WAVE accumulation, and WAVE complex loss increases Cadherin accumulation. To determine why Cadherin levels rise when WVE-1 is depleted, we use FRAP to analyze Cadherin dynamics and find that loss of WAVE as well as of the trafficking protein EHD-1/RME-1 increases Cadherin dynamics. EM studies in adults depleted of branched actin regulators support that WVE-1 maintains established junctions, presumably through its trafficking effect on Cadherin. Thus we propose a developmental model for junction formation where branched actin regulators are tightly interconnected with Cadherin junctions through their previously unappreciated role in Cadherin transport.