MYPT1 regulates contractility and microtubule acetylation to modulate integrin adhesions and matrix assembly.

MYPT1 regulates contractility and microtubule acetylation to modulate integrin adhesions and matrix assembly.
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DOI:
10.1038/ncomms4510
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发表时间:
2014-03-25
影响因子:
16.6
通讯作者:
Yamada, Kenneth M.
Yamada, Kenneth M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Joo, E. Emily;Yamada, Kenneth M.

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尽管我们对单个细胞骨架系统如何参与细胞迁移和分支形态形成等生理过程了解甚多,但对于这些不同的系统在聚合后如何积极协调它们的功能知之甚少。在这里,我们发现成纤维细胞和发育中的腺体相互协调细胞收缩性和微管乙酰化水平。我们发现这种平衡是通过肌凝蛋白磷酸酶靶亚基与肌凝蛋白轻链或微管去乙酰化酶HDAC6的相互作用实现的。这种收缩性和微管乙酰化的平衡通过调节α5β1整合素和纤维连接蛋白的表面密度来控制粘附成熟的进程。因此,我们提出收缩性和微管乙酰化之间的稳态平衡是由肌凝蛋白磷酸酶通过控制肌凝蛋白II和HDAC6的激活和失活来介导的。这可以调节α5β1整合素的表面密度,从而调节纤维连接蛋白基质的组装,并控制细胞迁移和分支形态发生的速率。
Although much is known about how individual cytoskeletal systems contribute to physiological processes such as cell migration and branching morphogenesis, little is known about how these different systems actively coordinate their functions after polymerization. Here we show that both fibroblasts and developing glands reciprocally coordinate levels of cellular contractility and microtubule acetylation. We find that this balance is achieved by interaction of the myosin phosphatase target subunit of myosin phosphatase with either myosin light chain or HDAC6, a microtubule deacetylase. This balance of contractility and microtubule acetylation controlled progression of adhesion maturation by regulating surface density of α5β1 integrin and fibronectin. Thus, we propose that a homeostatic balance between contractility and microtubule acetylation is mediated by myosin phosphatase via controlled activation and deactivation of myosin II and HDAC6. This regulates the surface density of α5β1 integrin to modulate fibronectin matrix assembly and governs rates of cell migration and branching morphogenesis.
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