Mechanism of microtubule stabilization by doublecortin
Mechanism of microtubule stabilization by doublecortin
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DOI：
10.1016/j.molcel.2004.06.009
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发表时间：
2004-06-18
期刊：
影响因子：
16
通讯作者：
Milligan, RA
中科院分区：
文献类型：
--
作者：
Moores, CA;Perderiset, M;Milligan, RA
神经元经历了一段神奇的旅程，从发育中的哺乳动物大脑的中心到大脑皮层的外层。双皮质素是微管细胞骨架的一个组成部分，在有丝分裂后神经元中是必不可少的，之所以被发现，是因为它的突变会破坏人类大脑的发育。双皮质素稳定微管并刺激其聚合，但与其他map没有同源性。我们使用电子显微镜来表征双皮质素的微管结合，并可视化其结合位点。双皮质素选择性地与13个原丝微管结合，并引起13个原丝微管的优先组装。当我们发现在构建微管的原丝之间存在双皮质素结合时，这种特异性得到了解释，这是一种以前未被描述的结合位点，是微管稳定的理想选择。这些数据揭示了双皮质素结合选择性的结构基础，并为其在成熟神经元中维持微管结构的作用提供了见解。
Neurons undertake an amazing journey from the center of the developing mammalian brain to the outer layers of the cerebral cortex. Doublecortin, a component of the microtubule cytoskeleton, is essential in postmitotic neurons and was identified because its mutation disrupts human brain development. Doublecortin stabilizes microtubules and stimulates their polymerization but has no homology with other MAPs. We used electron microscopy to characterize microtubule binding by doublecortin and visualize its binding site. Doublecortin binds selectively to 13 protofilament microtubules, its in vivo substrate, and also causes preferential assembly of 13 protofilament microtubules. This specificity was explained when we found that doublecortin binds between the protofilaments from which microtubules are built, a previously uncharacterized binding site that is ideal for microtubule stabilization. These data reveal the structural basis for doublecortin's binding selectivity and provide insight into its role in maintaining microtubule architecture in maturing neurons.