Regulation of nonmuscle myosin II by tropomyosin.
Regulation of nonmuscle myosin II by tropomyosin.
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DOI：
10.1021/bi500162z
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发表时间：
2014-06-24
期刊：
影响因子：
2.9
通讯作者：
Hitchcock-DeGregori SE
中科院分区：
文献类型：
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作者：
Barua B;Nagy A;Sellers JR;Hitchcock-DeGregori SE
肌动蛋白细胞骨架执行细胞功能，包括分裂、迁移、粘附和细胞内运输，这些功能需要多种肌动蛋白结合蛋白，包括肌球蛋白。我们的重点是II类非肌肉肌球蛋白亚型NMIIA、NMIIB和NMIIC，以及它们受肌动蛋白结合蛋白原肌球蛋白的调控。NMII肌球蛋白定位于不同种群的应力纤维和收缩环，这些结构与细胞迁移、粘附和细胞分裂所需的力产生有关。含有NMII肌球蛋白的应力纤维和收缩环也含有原肌球蛋白。四种哺乳动物基因编码超过40种原肌球蛋白。原肌凝蛋白抑制或激活肌动球蛋白MgATPase和运动取决于肌凝蛋白和原肌凝蛋白亚型。在体内，原肌球蛋白在细胞迁移、粘附、细胞分裂和NMII异构体定位中以异构体特异性的方式发挥作用。我们认为原肌球蛋白的特异性定位及其对NMII异构体定位的影响反映了NMII肌动球蛋白动力学和运动功能的调节。在这项研究中，我们比较了NMIIA、NMIIB和NMIIC以及骨骼肌肌球蛋白支持肌动蛋白丝运动的能力。原肌凝蛋白激活、抑制或不影响运动取决于肌凝蛋白，表明肌凝蛋白异构体是原肌凝蛋白对肌动球蛋白调节的异构体特异性作用的主要决定因素。NMII肌球蛋白激活非肌肉原肌球蛋白-肌动蛋白丝的运动与肌球蛋白MgATPase的Vmax增加相关，这意味着对肌球蛋白MgATPase有直接影响，而骨骼原肌球蛋白-肌动蛋白丝对Vmax或最大丝速没有影响。
The actin cytoskeleton carries out cellular functions, including division, migration, adhesion, and intracellular transport, that require a variety of actin binding proteins, including myosins. Our focus here is on class II nonmuscle myosin isoforms, NMIIA, NMIIB, and NMIIC, and their regulation by the actin binding protein, tropomyosin. NMII myosins are localized to different populations of stress fibers and the contractile ring, structures involved in force generation required for cell migration, adhesion, and cytokinesis. The stress fibers and contractile ring that contain NMII myosins also contain tropomyosin. Four mammalian genes encode more than 40 tropomyosins. Tropomyosins inhibit or activate actomyosin MgATPase and motility depending on the myosin and tropomyosin isoform. In vivo, tropomyosins play a role in cell migration, adhesion, cytokinesis, and NMII isoform localization in an isoform-specific manner. We postulate that the isoform-specific tropomyosin localization and effect on NMII isoform localization reflect modulation of NMII actomyosin kinetics and motile function. In this study, we compare the ability of different tropomyosin isoforms to support actin filament motility with NMIIA, NMIIB, and NMIIC as well as skeletal muscle myosin. Tropomyosins activated, inhibited, or had no effect on motility depending on the myosin, indicating that the myosin isoform is the primary determinant of the isoform-specific effect of tropomyosin on actomyosin regulation. Activation of motility of nonmuscle tropomyosin–actin filaments by NMII myosin correlates with an increased Vmax of the myosin MgATPase, implying a direct effect on the myosin MgATPase, in contrast to the skeletal tropomyosin–actin filament that has no effect on the Vmax or maximal filament velocity.