Myosin II isoforms identify distinct functional modules that support integrity of the epithelial zonula adherens.
Myosin II isoforms identify distinct functional modules that support integrity of the epithelial zonula adherens.
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肌球蛋白 II 亚型识别支持上皮粘附小带完整性的不同功能模块。
DOI：
10.1038/ncb2072
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发表时间：
2010-07
影响因子：
21.3
通讯作者：
Yap, Alpha S.
中科院分区：
文献类型：
--
作者：
Smutny, Michael;Cox, Hayley L.;Leerberg, Joanne M.;Kovacs, Eva M.;Conti, Mary Anne;Ferguson, Charles;Hamilton, Nicholas A.;Parton, Robert G.;Adelstein, Robert S.;Yap, Alpha S.
经典的钙粘蛋白受体与肌动蛋白细胞骨架的调节剂合作，以控制健康和疾病中的组织结构。在上皮细胞的顶端连接处，粘附小带（ZA）的钙粘蛋白环与相邻的肌动蛋白丝环偶联，以支持形态发生过程，例如组织整合和细胞形态。然而，在这些连接处协调粘附和细胞骨架的分子机制知之甚少。以前，我们确定了非肌肉肌球蛋白II作为Rho信号的目标，支持在哺乳动物上皮细胞中的钙粘蛋白连接。肌球蛋白II具有多种细胞功能，这些功能越来越多地归因于其不同亚型的特定生物物理特性和调节。在这里，我们报告，肌球蛋白II亚型有独特的和必要的作用，在钙粘蛋白连接。虽然三种哺乳动物肌球蛋白II亚型中的两种在ZA发现，但它们的定位受不同上游信号通路的调节。肌球蛋白IIA的连接定位需要E-cadherin粘附，Rho/ROCK和肌球蛋白轻链激酶，而连接肌球蛋白IIB依赖于Rap 1。此外，这些肌球蛋白II亚型通过不同的机制支持E-钙粘蛋白连接的完整性。肌球蛋白IIA RNA介导的干扰（RNAi）选择性地干扰E-钙粘蛋白在顶端ZA的积累，减少钙粘蛋白的嗜同性粘附和破坏钙粘蛋白聚集。相比之下，肌球蛋白IIB RNAi减少了纤维含量，改变了动力学，并增加了连接周围肌动蛋白环的侧向运动。因此，肌球蛋白IIA和IIB确定了两个不同的功能模块，具有不同的控制连接定位的上游信号和不同的功能效应。我们建议，这两个异构体为基础的模块合作，以协调粘附受体和F-肌动蛋白组织，形成顶端钙粘蛋白连接。
Classic cadherin receptors cooperate with regulators of the actin cytoskeleton to control tissue organization in health and disease. At the apical junctions of epithelial cells, the cadherin ring of the zonula adherens (ZA) couples with a contiguous ring of actin filaments,,to support morphogenetic processes such as tissue integration and cellular morphology,. However, the molecular mechanisms that coordinate adhesion and cytoskeleton at these junctions are poorly understood. Previously we identified non-muscle myosin II as a target of Rho signalling that supports cadherin junctions in mammalian epithelial cells. Myosin II has various cellular functions, which are increasingly attributable to the specific biophysical properties and regulation of its different isoforms. Here we report that myosin II isoforms have distinct and necessary roles at cadherin junctions. Although two of the three mammalian myosin II isoforms are found at the ZA, their localization is regulated by different upstream signalling pathways. Junctional localization of myosin IIA required E-cadherin adhesion, Rho/ROCK and myosin light-chain kinase, whereas junctional myosin IIB depended on Rap1. Further, these myosin II isoforms support E-cadherin junction integrity by different mechanisms. Myosin IIA RNA-mediated interference (RNAi) selectively perturbed the accumulation of E-cadherin in the apical ZA, decreased cadherin homophilic adhesion and disrupted cadherin clustering. In contrast, myosin IIB RNAi decreased filament content, altered dynamics, and increased the lateral movement of the perijunctional actin ring. Myosin IIA and IIB therefore identify two distinct functional modules, with different upstream signals that control junctional localization, and distinct functional effects. We propose that these two isoform-based modules cooperate to coordinate adhesion receptor and F-actin organization to form apical cadherin junctions.
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DOI：
10.1083/jcb.100.1.327
发表时间：
1985-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Boller K;Vestweber D;Kemler R
通讯作者：
Kemler R
影响因子：
7.8
作者：
Helwani, FM;Kovacs, EM;Yap, AS
通讯作者：
Yap, AS
影响因子：
3.3
作者：
Shewan, AM;Maddugoda, M;Yap, AS
通讯作者：
Yap, AS
在哺乳动物上皮细胞中钙粘着蛋白细胞接触的形态发生过程中，肌球蛋白VI和VINCULIN合作。
DOI：
10.1083/jcb.200612042
发表时间：
2007-07-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Maddugoda MP;Crampton MS;Shewan AM;Yap AS
通讯作者：
Yap AS
影响因子：
21.3
作者：
Kametani, Yoshiko;Takeichi, Masatoshi
通讯作者：
Takeichi, Masatoshi