Sidekick dynamically rebalances contractile and protrusive forces to control tissue morphogenesis.
Sidekick dynamically rebalances contractile and protrusive forces to control tissue morphogenesis.
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DOI：
10.1083/jcb.202107035
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发表时间：
2022-05-02
期刊：
影响因子：
--
通讯作者：
Hatini V
中科院分区：
文献类型：
--
作者：
Malin J;Rosa Birriel C;Astigarraga S;Treisman JE;Hatini V
Malin等人的研究表明，亲同质粘附分子Sidekick与WAVE调节复合体和三细胞粘附连接处的Polychaetoid/Zonula occludence-1交替相互作用，动态地重新平衡对立的伸缩力，这些伸缩力反复扩大和收缩细胞接触，以维持细胞间接触并确保适当的上皮重塑。收缩肌动蛋白和突起分支的f -肌动蛋白网络在动态平衡中相互作用，反复收缩和扩大顶端细胞接触来组织发育中的果蝇视网膜上皮。先前我们发现免疫球蛋白超家族蛋白Sidekick （Sdk）通过将肌动蛋白结合蛋白Polychaetoid （Pyd）募集到顶点来促进收缩。在这里，我们发现随着收缩期间张力的增加，Sdk逐渐在顶点积累，在那里它切换到招募WAVE调节复合体（WRC）以促进肌动蛋白分支和突出。Sdk使用相同的c端基序交替地与WRC和Pyd交互。随着突起的增加，顶点处的Sdk和WRC水平降低，而Pyd水平增加，为另一轮收缩铺平了道路。因此，由于与顶点的动态关联以及与收缩和突出效应物的可互换关联，Sdk对于控制形成上皮的收缩和扩张之间的平衡至关重要。
Malin et al. show that the homophilic adhesion molecule Sidekick interacts alternately with the WAVE regulatory complex and with Polychaetoid/Zonula occludence-1 at tricellular adherens junctions to dynamically rebalance opposing protrusive and contractile forces that repeatedly expand and contract cell contacts to maintain cell–cell contacts and ensure proper epithelial remodeling. Contractile actomyosin and protrusive branched F-actin networks interact in a dynamic balance, repeatedly contracting and expanding apical cell contacts to organize the epithelium of the developing fly retina. Previously we showed that the immunoglobulin superfamily protein Sidekick (Sdk) contributes to contraction by recruiting the actin binding protein Polychaetoid (Pyd) to vertices. Here we show that as tension increases during contraction, Sdk progressively accumulates at vertices, where it toggles to recruit the WAVE regulatory complex (WRC) to promote actin branching and protrusion. Sdk alternately interacts with the WRC and Pyd using the same C-terminal motif. With increasing protrusion, levels of Sdk and the WRC decrease at vertices while levels of Pyd increase paving the way for another round of contraction. Thus, by virtue of dynamic association with vertices and interchangeable associations with contractile and protrusive effectors, Sdk is central to controlling the balance between contraction and expansion that shapes this epithelium.
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