Hundt Nikolas, Steffen Walter, Pathan-Chhatbar Salma, Taft Manuel H, Manstein Dietmar J
Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Molecular and Cell Physiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Sci Rep. 2016 Feb 5;6:20554. doi: 10.1038/srep20554.
Tropomyosin isoforms play an important role in the organisation of cytoplasmic actomyosin complexes in regard to function and cellular localisation. In particular, Tpm4.2 is upregulated in rapidly migrating cells and responsible for the specific recruitment of the cytoplasmic class-2 myosin NM-2A to actin filaments during the formation of stress fibres. Here, we investigate how the decoration of F-actin with Tpm4.2 affects the motor properties of NM-2A under conditions of low and high load. In the absence of external forces, decoration of actin filaments with Tpm4.2 does not affect the gated release of ADP from NM-2A and the transition from strong to weak actin-binding states. In the presence of resisting loads, our results reveal a marked increase in the mechanosensitive gating between the leading and trailing myosin head. Thereby, the processive behaviour of NM-2A is enhanced in the presence of resisting loads. The load- and Tpm4.2-induced changes in the functional behaviour of NM-2A are in good agreement with the role of this myosin in the context of stress fibres and the maintenance of cellular tension.
原肌球蛋白同工型在细胞质肌动球蛋白复合物的功能组织和细胞定位方面发挥着重要作用。特别是,Tpm4.2在快速迁移的细胞中上调,并在应力纤维形成过程中负责将细胞质2类肌球蛋白NM-2A特异性募集到肌动蛋白丝上。在此,我们研究了在低负荷和高负荷条件下,用Tpm4.2修饰F-肌动蛋白如何影响NM-2A的运动特性。在没有外力的情况下,用Tpm4.2修饰肌动蛋白丝不会影响ADP从NM-2A的门控释放以及从强肌动蛋白结合状态到弱肌动蛋白结合状态的转变。在存在阻力负荷的情况下,我们的结果显示,领先和滞后的肌球蛋白头部之间的机械敏感门控显著增加。因此,在存在阻力负荷的情况下,NM-2A的持续性行为得到增强。负荷和Tpm4.2诱导的NM-2A功能行为变化与这种肌球蛋白在应力纤维背景下的作用以及细胞张力的维持高度一致。
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