Department of Physics & Astronomy, University of Utah, Salt Lake City, UT, 84112, USA.
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA.
Biochem Biophys Res Commun. 2020 Jul 30;528(3):528-530. doi: 10.1016/j.bbrc.2020.05.157. Epub 2020 Jun 4.
Cytoskeletal transport in cells is driven by enzymes whose activity shows sensitive, typically Arrhenius, dependence on temperature. Often, the duration and outcome of cargo transport is determined by the relative success of kinesin vs. dynein motors, which can simultaneously bind to individual cargos and move in opposite direction on microtubules. The question of how kinesin and dynein activity remain coupled over the large temperature ranges experienced by some cells is one of clear biological relevance. We report a break in the Arrhenius behavior of both kinesin-1 and kinesin-3 enzymatic activity at 4.7 °C and 10.5 °C, respectively. Further, we report that this transition temperature significantly changes as a function of chemical background: addition of 200 mM TMAO increases transition temperatures by ∼6 °C in all cases. Our results show that Arrhenius trend breaks are common to all cytoskeletal motors and open a broad question of how such activity transitions are regulated in vivo. STATEMENT OF SIGNIFICANCE: Many cytoskeletal motors studied to date follow Arrhenius kinetics, at least from room temperature up to mammalian body temperature. However the thermal dynamic range is typically finite, and breaks in Arrhenius trends are commonly observed at biologically relevant temperatures. Here we report that the thermal dynamic range of kinesins is also limited and moreover that the location of the Arrhenius break for kinesins can shift significantly based on chemical backgrounds. This implies that the balance of multiple motor cargo transport along the cytoskeleton is far more tunable as a function of temperature than previously appreciated.
细胞中的细胞骨架运输是由酶驱动的,其活性对温度表现出敏感的、典型的 Arrhenius 依赖性。通常,货物运输的持续时间和结果取决于驱动蛋白和动力蛋白马达的相对成功,它们可以同时结合到单个货物上,并在微管上向相反的方向移动。驱动蛋白和动力蛋白活性如何在一些细胞经历的大温度范围内保持耦合,这是一个具有明显生物学相关性的问题。我们报告了驱动蛋白-1 和驱动蛋白-3 的酶活性的 Arrhenius 行为分别在 4.7°C 和 10.5°C 处发生中断。此外,我们报告说,这种转变温度会随着化学背景的变化而显著改变:在所有情况下,添加 200mM TMAO 都会将转变温度分别提高约 6°C。我们的结果表明,Arrhenius 趋势的中断是所有细胞骨架马达共有的,并提出了一个广泛的问题,即在体内如何调节这种活性转变。
迄今为止,许多研究过的细胞骨架马达至少遵循 Arrhenius 动力学,至少从室温到哺乳动物体温都是如此。然而,热动力学范围通常是有限的,并且在生物相关温度下经常观察到 Arrhenius 趋势的中断。在这里,我们报告说,驱动蛋白的热动力学范围也是有限的,而且驱动蛋白的 Arrhenius 中断的位置可以根据化学背景显著移动。这意味着,沿着细胞骨架的多个马达货物运输的平衡作为温度的函数比以前认为的要灵活得多。