Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity.
Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity.
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DOI：
10.1038/ncomms12187
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发表时间：
2016-07-13
影响因子：
16.6
通讯作者：
Lüders J
中科院分区：
文献类型：
--
作者：
Sánchez-Huertas C;Freixo F;Viais R;Lacasa C;Soriano E;Lüders J
神经元表现出高度极化的微管网络，介导整个细胞质中的运输，对神经元分化和功能至关重要。在新生的迁移神经元中，微管网络由中心体组织。然而，在神经元成熟过程中，中心体逐渐失去这种活性，而微管在更成熟的神经元中是如何组织的仍然知之甚少。在这里，我们证明有丝分裂后神经元中的微管组织强烈依赖于由 augmin 和成核剂 γTuRC 介导的非中心体成核。任一复合物的破坏不仅会降低微管密度，还会降低微管成束。这些微管缺陷会损害神经突的形成，干扰轴突的规格和生长，并破坏轴突的运输。在轴突中，奥格明不仅介导微管的成核，而且确保其均匀的末端方向。因此，最初在有丝分裂细胞中鉴定出的 augmin-γTuRC 模块通常可用于生成和维持具有特定极性的微管构型。 在成熟的神经元中，中心体不再充当主要的微管组织者，并且尚不清楚有序的微管阵列是如何组装的。在这里，作者表明，在有丝分裂后神经元中，这一过程依赖于蛋白质复合物 augmin 和成核剂 gamma-TuRC 介导的非中心体成核。
Neurons display a highly polarized microtubule network that mediates trafficking throughout the extensive cytoplasm and is crucial for neuronal differentiation and function. In newborn migrating neurons, the microtubule network is organized by the centrosome. During neuron maturation, however, the centrosome gradually loses this activity, and how microtubules are organized in more mature neurons remains poorly understood. Here, we demonstrate that microtubule organization in post-mitotic neurons strongly depends on non-centrosomal nucleation mediated by augmin and by the nucleator γTuRC. Disruption of either complex not only reduces microtubule density but also microtubule bundling. These microtubule defects impair neurite formation, interfere with axon specification and growth, and disrupt axonal trafficking. In axons augmin does not merely mediate nucleation of microtubules but ensures their uniform plus end-out orientation. Thus, the augmin-γTuRC module, initially identified in mitotic cells, may be commonly used to generate and maintain microtubule configurations with specific polarity. In mature neurons the centrosome no longer functions as the main microtubule organizer and it is unclear how ordered microtubule arrays are assembled. Here, the authors show that in post-mitotic neurons this process depends on non-centrosomal nucleation mediated by the protein complex augmin and the nucleator gamma-TuRC.