Yes-associated protein impacts adherens junction assembly through regulating actin cytoskeleton organization
Yes-associated protein impacts adherens junction assembly through regulating actin cytoskeleton organization
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DOI：
10.1152/ajpgi.00027.2016
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发表时间：
2016-09-01
影响因子：
4.5
通讯作者：
Anders, Robert A.
中科院分区：
文献类型：
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作者：
Bai, Haibo;Zhu, Qingfeng;Anders, Robert A.
Hippo通路效应物Yes-associated protein （YAP）通过促进细胞增殖和抑制细胞凋亡来调节肝脏大小。然而，最近的体内研究表明，除了控制增殖和凋亡外，YAP还具有重要的细胞功能。转基因YAP在小鼠肝细胞中的表达导致严重的黄疸。对黄疸的一种可能解释是，防止胆汁渗漏到血液中的粘附连接处存在缺陷。的确，转基因肝的E-cadherin免疫染色和胆管电镜检查显示了异常的粘附连接结构。使用来自Yap转基因肝脏和Yap基因敲除肝脏的原代肝细胞，我们发现Yap通过调节细胞肌动蛋白结构，包括其机械特性（弹性和皮质张力），拮抗e -cadherin介导的细胞-细胞连接组装。在机制上，我们发现YAP通过上调非肌球蛋白轻链表达和细胞ATP生成来促进收缩肌动蛋白结构的形成。因此，通过调节肌动球蛋白组织，YAP可能影响许多肌动球蛋白依赖的细胞特性，包括粘附、膜突出、扩张、形态、皮质张力和弹性，这些特性反过来决定细胞分化和组织形态发生。
The Hippo pathway effector Yes-associated protein (YAP) regulates liver size by promoting cell proliferation and inhibiting apoptosis. However, recent in vivo studies suggest that YAP has important cellular functions other than controlling proliferation and apoptosis. Transgenic YAP expression in mouse hepatocytes results in severe jaundice. A possible explanation for the jaundice could be defects in adherens junctions that prevent bile from leaking into the blood stream. Indeed, immunostaining of E-cadherin and electron microscopic examination of bile canaliculi of Yap transgenic livers revealed abnormal adherens junction structures. Using primary hepatocytes from Yap transgenic livers and Yap knockout livers, we found that YAP antagonizes E-cadherin-mediated cell-cell junction assembly by regulating the cellular actin architecture, including its mechanical properties (elasticity and cortical tension). Mechanistically, we found that YAP promoted contractile actin structure formation by upregulating nonmuscle myosin light chain expression and cellular ATP generation. Thus, by modulating actomyosin organization, YAP may influence many actomyosin-dependent cellular characteristics, including adhesion, membrane protrusion, spreading, morphology, and cortical tension and elasticity, which in turn determine cell differentiation and tissue morphogenesis.