Feizabadi Mitra Shojania, Hernandez Marcos A V, Breslin Jane B, Akintola Ibukunoluwa I
Department of Physics, Seton Hall University, 400 South Orange Ave., South Orange, NJ 07079, USA.
Biochem Biophys Rep. 2019 Jan 9;17:151-156. doi: 10.1016/j.bbrep.2018.12.010. eCollection 2019 Mar.
Growing evidence continues to point toward the critical role of beta tubulin isotypes in regulating some intracellular functions. Changes that were observed in the microtubules' intrinsic dynamics, the way they interact with some chemotherapeutic agents, or differences on translocation specifications of some molecular motors along microtubules, were associated to their structural uniqueness in terms of beta tubulin isotype distributions. These findings suggest that the effects of microtubule associated proteins (MAPs) may also vary on structurally different microtubules. Among different microtubule associated proteins, Tau proteins, which are known as neuronal MAPs, bind to beta tubulin, stabilize microtubules, and consequently promote their polymerizations. In this study, in a set of well controlled experiments, the direct effect of Tau proteins on the polymerization of two structurally different microtubules, porcine brain and breast cancer (MCF7), were tested and compared. Remarkably, we found that in contrast with the promoted effect of Tau proteins on brain microtubules' polymerization, MCF7 expressed a demoted polymerization while interacting with Tau proteins. This finding can potentially be a novel insight into the mechanism of drug resistance in some breast cancer cells. It has been reported that microtubules show destabilizing behavior in some MCF7 cells with overexpression of Tau protein when treated with a microtubules' stabilizing agent, Taxol. This behavior has been classified by others as drug resistance, but it may instead be potentially caused by a competition between the destabilizing effect of the Tau protein and the stabilizing effect of the drug on MCF7 microtubules. Also, we quantified the polarization coefficient of MCF7 microtubules in the presence and absence of Tau proteins by the electro-orientation method and compared the values. The two significantly different values obtained can possibly be one factor considered to explain the effect of Tau proteins on the polymerization of MCF7 microtubules.
越来越多的证据不断表明β微管蛋白异构体在调节某些细胞内功能方面的关键作用。在微管的内在动力学、它们与某些化疗药物相互作用的方式，或者某些分子马达沿微管的转运特性方面观察到的变化，与它们在β微管蛋白异构体分布方面的结构独特性有关。这些发现表明，微管相关蛋白（MAPs）的作用在结构不同的微管上也可能有所不同。在不同的微管相关蛋白中，被称为神经元MAPs的Tau蛋白与β微管蛋白结合，稳定微管，从而促进其聚合。在本研究中，在一组严格控制的实验中，测试并比较了Tau蛋白对两种结构不同的微管（猪脑微管和乳腺癌（MCF7）微管）聚合的直接影响。值得注意的是，我们发现，与Tau蛋白对脑微管聚合的促进作用相反，MCF7在与Tau蛋白相互作用时表现出聚合作用减弱。这一发现可能为某些乳腺癌细胞的耐药机制提供新的见解。据报道，在用微管稳定剂紫杉醇处理时，一些Tau蛋白过度表达的MCF7细胞中微管表现出不稳定行为。其他人将这种行为归类为耐药性，但它可能反而潜在地是由Tau蛋白的去稳定作用和药物对MCF7微管的稳定作用之间的竞争引起的。此外，我们通过电取向方法定量了有或没有Tau蛋白时MCF7微管的极化系数，并比较了这些值。获得的两个显著不同的值可能是解释Tau蛋白对MCF7微管聚合作用的一个因素。
