Human Microtubule-Associated-Protein Tau Regulates the Number of Protofilaments in Microtubules: A Synchrotron X-Ray Scattering Study
Human Microtubule-Associated-Protein Tau Regulates the Number of Protofilaments in Microtubules: A Synchrotron X-Ray Scattering Study
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DOI：
10.1016/j.bpj.2009.04.047
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发表时间：
2009-07-22
影响因子：
3.4
通讯作者：
Safinya, C. R.
中科院分区：
文献类型：
--
作者：
Choi, M. C.;Raviv, U.;Safinya, C. R.
微管 (MT) 是真核细胞骨架的主要组成部分，是 25 nm 的蛋白质纳米管，其壁由 αβ 异二聚微管蛋白组装而成的原丝组成。在神经细胞中，微管相关蛋白 (MAP) tau 的不同亚型调节微管蛋白组装和 MT 稳定性。使用同步加速器小角 X 射线散射 (SAXS)，我们研究了所有六种天然存在的中枢神经系统 tau 异构体对紫杉醇稳定的 MT 组装结构的影响。最值得注意的是，我们发现 tau 调节 MT 中原丝数量的分布，这反映在观察到的 MT 平均半径 < R-MT > 随着 Phi（tau/微管蛋白-晚餐摩尔比）的增加而增加。在实验分散中，<R-MT>的变化似乎与异构体无关。值得注意的是，当 0 < Phi < 0.2 时，观察到 <R-MT > 快速增加，而当 Phi 在 0.2-0.5 之间时则饱和。因此，tau蛋白结合上的微管蛋白晚餐的局部形状扭曲，其覆盖范围远小于单层，以原丝的规模共同分布在许多晚餐上。这意味着 tau 调节原丝的形状，从而调节 MT 的自发曲率 C-o(MT)，从而导致曲率 C-MT (=1/R-MT) 的变化。这些发现的一个重要生物学意义是 tau 可能具有变构作用，其中 tau 诱导的 MT 表面形状变化可能会影响神经元中存在的其他 MAP 的 MT 结合活性。此外，这些结果提供了对 tau 对 MT 弹性特性调节的深入了解，也可能影响需要径向尺寸控制纳米管的生物材料应用。
Microtubules (MTs), a major component of the eukaryotic cytoskeleton, are 25 nm protein nanotubes with walls comprised of assembled protofilaments built from alpha beta heterodimeric tubulin. In neural cells, different isoforms of the microtubule-associated-protein (MAP) tau regulate tubulin assembly and MT stability. Using synchrotron small angle x-ray scattering (SAXS), we have examined the effects of all six naturally occurring central nervous system tau isoforms on the assembly structure of taxol-stabilized MTs. Most notably, we found that tau regulates the distribution of protofilament numbers in MTs as reflected in the observed increase in the average radius < R-MT > of MTs with increasing Phi, the tau/tubulin-dinner molar ratio. Within experimental scatter, the change in < R-MT > seems to be isoform independent. Significantly, < R-MT > was observed to rapidly increase for 0 < Phi < 0.2 and saturate for Phi between 0.2-0.5. Thus, a local shape distortion of the tubulin dinner on tau binding, at coverages much less than a monolayer, is spread collectively over many dinners on the scale of protofilaments. This implies that tau regulates the shape of protofilaments and thus the spontaneous curvature C-o(MT) of MTs leading to changes in the curvature C-MT (=1/R-MT). An important biological implication of these findings is a possible allosteric role for tau where the tau-induced shape changes of the MT surface may effect the MT binding activity of other MAPs present in neurons. Furthermore, the results, which provide insight into the regulation of the elastic properties of MTs by tau, may also impact biomaterials applications requiring radial size-controlled nanotubes.