Nonmuscle myosin IIA and IIB differently suppress microtubule growth to stabilize cell morphology

Nonmuscle myosin IIA and IIB differently suppress microtubule growth to stabilize cell morphology
复制标题

非肌肉肌球蛋白 IIA 和 IIB 以不同方式抑制微管生长以稳定细胞形态

DOI:
10.1093/jb/mvz082
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发表时间:
2020
期刊:
The Journal of Biochemistry
影响因子:
--
通讯作者:
Takahashi M.
Takahashi M.
中科院分区:
--
文献类型:
--
作者:
Sato Y.;Kamijo K.;Tsutsumi M.;Murakami Y.;Takahashi M.

文献摘要

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细胞骨架动力学的精确调节在许多基本的细胞过程中是重要的,如细胞形状的确定。肌动蛋白和微管(MT)细胞骨架相互调节其稳定性和动力学。非肌肉肌球蛋白II(NMII)是介导肌动蛋白-MT串扰的候选蛋白。NMII调节肌动蛋白丝的稳定性和动力学以控制细胞形态。此外,以前的报告表明,NMII依赖的细胞收缩调节MT动力学,和MT也控制细胞形态;然而,详细的机制,NMII调节MT动力学和肌动蛋白动力学,MT动力学和细胞形态之间的关系仍然不清楚。本研究探讨了两个良好的特点NMII亚型,NMIIA和NMIIB的MT生长动力学和细胞形态的调节的作用。我们进行了RNAi和药物实验,并证明了NMII亚型特异性机制-NMIIA依赖的细胞收缩性上调了一些哺乳动物透明相关蛋白(mDia)的表达,抑制MT动力学; NMIIB依赖的肌动蛋白解聚抑制MT生长独立于细胞收缩性。NMIIA或NMIIB的耗尽导致细胞形态动力学的增加,这是由MT动力学的扰动缓解。因此,细胞形态的匪II依赖性控制显著依赖于MT动力学。
Precise regulation of cytoskeletal dynamics is important in many fundamental cellular processes such as cell shape determination. Actin and microtubule (MT) cytoskeletons mutually regulate their stability and dynamics. Nonmuscle myosin II (NMII) is a candidate protein that mediates the actin–MT crosstalk. NMII regulates the stability and dynamics of actin filaments to control cell morphology. Additionally, previous reports suggest that NMII-dependent cellular contractility regulates MT dynamics, and MTs also control cell morphology; however, the detailed mechanism whereby NMII regulates MT dynamics and the relationship among actin dynamics, MT dynamics and cell morphology remain unclear. The present study explores the roles of two well-characterized NMII isoforms, NMIIA and NMIIB, on the regulation of MT growth dynamics and cell morphology. We performed RNAi and drug experiments and demonstrated the NMII isoform-specific mechanisms—NMIIA-dependent cellular contractility upregulates the expression of some mammalian diaphanous-related formin (mDia) proteins that suppress MT dynamics; NMIIB-dependent inhibition of actin depolymerization suppresses MT growth independently of cellular contractility. The depletion of either NMIIA or NMIIB resulted in the increase in cellular morphological dynamicity, which was alleviated by the perturbation of MT dynamics. Thus, the NMII-dependent control of cell morphology significantly relies on MT dynamics.