Microtubule acetylation promotes kinesin-1 binding and transport
Microtubule acetylation promotes kinesin-1 binding and transport
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DOI：
10.1016/j.cub.2006.09.014
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发表时间：
2006-11-07
期刊：
影响因子：
9.2
通讯作者：
Verhey, Kristen J.
中科院分区：
文献类型：
--
作者：
Reed, Nathan A.;Cai, Dawen;Verhey, Kristen J.
长距离细胞内递送由驱动蛋白和动力蛋白马达蛋白驱动，其沿着沿着微管轨道运送货物[1，2]。目前的模型假设，定向贩运是由已知的生物物理特性，这些马达驱动蛋白一般移动到微管在细胞周边的正端，而细胞质动力蛋白移动到细胞中心的负端。然而，这些模型不足以解释如何实现极化蛋白质运输到亚细胞结构域。我们发现，驱动蛋白-1货物蛋白JNK相互作用蛋白1（JIP 1）是本地化的，只有一个子集的神经突起在培养的神经元细胞。极化贩运的机制似乎涉及优先识别微管含有特定的翻译后修饰（PTM）的驱动蛋白-1马达结构域。使用遗传方法消除特定的PTM，我们表明，一个单一的修改，α-微管蛋白乙酰化在赖氨酸-40的损失，影响驱动蛋白-1的结合和运动在体外。此外，增加微管乙酰化的药物治疗导致JIP 1的驱动蛋白-1转运重定向到体内几乎所有的神经突尖端。这些结果表明，微管PTMs是不同的微管群体的重要标志物，它们的作用是控制马达蛋白的运输。
Long-distance intracellular delivery is driven by kinesin and dynein motor proteins that ferry cargoes along microtubule tracks [1, 2]. Current models postulate that directional trafficking is governed by known biophysical properties of these motors-kinesins generally move to the plus ends of microtubules in the cell periphery, whereas cytoplasmic dynein moves to the minus ends in the cell center. However, these models are insufficient to explain how polarized protein trafficking to subcellular domains is accomplished. We show that the kinesin-1 cargo protein JNK-interacting protein 1 (JIP1) is localized to only a subset of neurites in cultured neuronal cells. The mechanism of polarized trafficking appears to involve the preferential recognition of microtubules containing specific posttranslational modifications (PTMs) by the kinesin-1 motor domain. Using a genetic approach to eliminate specific PTMs, we show that the loss of a single modification, alpha-tubulin acetylation at Lys-40, influences the binding and motility of kinesin-1 in vitro. In addition, pharmacological treatments that increase microtubule acetylation cause a redirection of kinesin-1 transport of JIP1 to nearly all neurite tips in vivo. These results suggest that microtubule PTMs are important markers of distinct microtubule populations and that they act to control motor-protein trafficking.