Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens.
Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens.
复制标题
DOI：
10.1016/j.cub.2014.06.028
复制
发表时间：
2014-08-04
期刊：
影响因子：
9.2
通讯作者：
Yap, Alpha S.
中科院分区：
文献类型：
--
作者：
Leerberg, Joanne M.;Gomez, Guillermo A.;Verma, Suzie;Moussa, Elliott J.;Wu, Selwin K.;Priya, Rashmi;Hoffman, Brenton D.;Grashoff, Carsten;Schwartz, Martin A.;Yap, Alpha S.
基于肌动蛋白的收缩作用于钙粘蛋白连接以支持组织完整性和形态发生。上皮粘附小带（ZA）的肌动球蛋白装置是通过协调连接肌动蛋白组装和肌球蛋白II激活而建立的。然而，肌球蛋白和肌动蛋白丝之间的物理相互作用是必要的收缩性可以诱导肌动蛋白丝的周转，可能会损害收缩装置本身。我们现在确定张力敏感肌动蛋白组装作为一个细胞解决方案，这个设计悖论。我们发现，连接肌动蛋白组装维持在已建立的连接和收缩性时，增加收缩性刺激。潜在的机制需要粘着斑蛋白的张力敏感的招聘到ZA。反过来，Escherulin直接招募Mena/VASP蛋白以支持连接肌动蛋白组装。通过将Mena/VASP与黏着斑蛋白或异位靶向Mena/VASP结合到连接处的策略相结合，我们表明张力敏感性肌动蛋白组装对于ZA处的连接完整性和有效收缩性是必要的。我们的结论是，张力敏感的调节肌动蛋白组装代表了上皮细胞的机制，以解决潜在的设计矛盾，是固有的方式，连接肌动球蛋白系统组装。这强调了肌动蛋白支架本身的维持和调节影响细胞如何产生收缩张力。
Actomyosin-based contractility acts on cadherin junctions to support tissue integrity and morphogenesis. The actomyosin apparatus of the epithelial zonula adherens (ZA) is built by coordinating junctional actin assembly with Myosin II activation. However, the physical interaction between Myosin and actin filaments that is necessary for contractility can induce actin filament turnover, potentially compromising the contractile apparatus itself. We now identify tension-sensitive actin assembly as one cellular solution to this design paradox. We show that junctional actin assembly is maintained by contractility in established junctions and increases when contractility is stimulated. The underlying mechanism entails the tension-sensitive recruitment of vinculin to the ZA. Vinculin, in turn, directly recruits Mena/VASP proteins to support junctional actin assembly. By combining strategies that uncouple Mena/VASP from vinculin or ectopically target Mena/VASP to junctions, we show that tension-sensitive actin assembly is necessary for junctional integrity and effective contractility at the ZA. We conclude that tension-sensitive regulation of actin assembly represents a mechanism for epithelial cells to resolve potential design contradictions that are inherent in the way that the junctional actomyosin system is assembled. This emphasizes that maintenance and regulation of the actin scaffolds themselves influence how cells generate contractile tension.
登录
查看更多内容
Vinculin磷酸化差异地调节了细胞 - 细胞和细胞矩阵粘附处的机械转导。
DOI：
10.1083/jcb.201309092
发表时间：
2014-04-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bays JL;Peng X;Tolbert CE;Guilluy C;Angell AE;Pan Y;Superfine R;Burridge K;DeMali KA
通讯作者：
DeMali KA
影响因子：
6.6
作者：
Carisey, Alex;Ballestrem, Christoph
通讯作者：
Ballestrem, Christoph
影响因子：
4.6
作者：
Gates, Julie;Mahaffey, James P.;Peifer, Mark
通讯作者：
Peifer, Mark
影响因子：
3.7
作者：
Miyake, Yuka;Inoue, Naoko;Yonemura, Shigenobu
通讯作者：
Yonemura, Shigenobu
影响因子：
4.8
作者：
Chen, Hui;Choudhury, Dilshad M.;Craig, Susan W.
通讯作者：
Craig, Susan W.