Microtubule dynamics: 50 years after the discovery of tubulin and still going strong.
Microtubule dynamics: 50 years after the discovery of tubulin and still going strong.
复制标题
微管动力学：微管蛋白发现 50 年后仍然强劲。
DOI：
10.1091/mbc.e16-12-0833
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发表时间：
2017
影响因子：
3.3
通讯作者：
Roll-Mecak,Antonina
中科院分区：
文献类型：
--
作者：
Pigino,Gaia;Roll-Mecak,Antonina
微型对称“微管动力学”的演讲者从微管领域的创始成员到开始科学之旅的研究生。会议涵盖了广泛的主题，从微管的结构和动力学的基本问题，到分子马达在重建系统中的行为，再到微管调节剂在神经再生中的治疗潜力。在Borisy和Taylor发现微管蛋白的50年后，这次会议证明了微管仍然有许多秘密。Dick McIntosh（科罗拉多大学，博尔德）在会议开始时展示了微管的生长尖端，如电子断层扫描所见，显示了体外和体内从聚合物轴卷曲出来的原丝。曲率最大的原丝尖端和足够低的近壁的一个不断增长的微管，以允许二聚体之间的吸引力驱动原丝拉直。这种微管生长的机制不同于几种已发表的模型，肯定会催化微管蛋白聚合途径的新面貌。Annapurna Vemu（Roll-Mecak实验室，美国国立卫生研究院神经疾病和中风研究所）解决了微管生物学中的一个老问题，即微管蛋白亚型组成如何影响微管动力学。通过使用从不同细胞类型纯化的微管蛋白以及重组表达的单一同种型人微管蛋白进行无标记的体外动态测定，Vemu表明不同的微管蛋白同种型具有显著不同的动态参数，并且微管动力学可以与同种型组成成比例地变化。Anne Straube（英国考文垂的沃里克大学）发现了三种哺乳动物微管末端结合蛋白（EB 1、EB 2和EB 3）在生长的微管尖端的不同定位。Straube的研究小组发现，尖端结合特异性的背后是EB在两个原丝之间结合并感知两侧β-微管蛋白的特定核苷酸状态的能力。两个演讲集中在微管成核。加勒特格林南（罗恩维尔和大卫阿加德实验室，加州大学，旧金山弗朗西斯科）提出了电子冷冻断层扫描重建中心粒从果蝇和哺乳动物细胞系，其中含有双重和三重微管，分别。虽然它们的整体九重对称结构是保守的，但重建表明，在没有C-微管的情况下，果蝇中心粒双联体通过A/A-接头连接，与哺乳动物中心粒中的A/C-接头在位置和结构上都不同。Greenan假设，这种结构上的差异维持了果蝇中心粒募集中心粒周围物质和微管成核的能力。Jan Brugués（马克斯·普朗克分子细胞生物学和遗传学研究所，德累斯顿，德国）通过测量微管成核来研究纺锤体的尺寸上限。通过激光烧蚀测量负末端与耗尽实验和数学建模的结合，Brugués提出了活性成核剂的量通过微管估计的微管成核来设定纺锤体的大小和质量的证据。然后，会议转向基于微管的马达。Stephen Norris（范德比尔特大学Ohi和Zanic实验室）专注于微管负端，特别是驱动蛋白14（人类的HSET/KIFC 1）在将额外中心体聚焦到两极中的作用。使用基于单分子荧光的测定，他表明可溶性...
The Minisymposium “Microtubule Dynamics” featured speakers ranging from a founding member of the microtubule field to graduate students embarking on their scientific journeys. The session spanned a broad range of topics, from fundamental questions about the structure and dynamics of microtubules, to the behavior of molecular motors in reconstituted systems, to the therapeutic potential of microtubule regulators in neuroregeneration. Fifty years after the discovery of tubulin by Borisy and Taylor, this session was proof that microtubules still have many secrets. Dick McIntosh (University of Colorado, Boulder) kicked off the session by showing that the growing tips of microtubules, as seen by electron tomography, displayed protofilaments that curled out from the polymer axis both in vitro and in vivo. Curvatures were greatest at the protofilament tips and low enough near the wall of a growing microtubule to allow attractive forces between dimers to drive protofilament straightening. This mechanism of microtubule growth differs from several published models and will certainly catalyze a new look at the tubulin polymerization pathway. Annapurna Vemu (Roll-Mecak laboratory, National Institute of Neurological Disorders and Stroke, National Institutes of Health) tackled an old problem in microtubule biology of how tubulin isoform composition influences microtubule dynamics. By performing label-free in vitro dynamic assays with tubulin purified from different cell types as well as recombinantly expressed single-isoform human tubulin, Vemu showed that different tubulin isoforms have dramatically different dynamic parameters and that microtubule dynamics can vary proportionally with isoform composition. Anne Straube (University of Warwick, Coventry, United Kingdom) uncovered a differential positioning of the three mammalian microtubule end-binding proteins (EB1, EB2, and EB3) from the growing microtubule tip. Straube’s team found that behind the tip-binding specificities is the ability of EBs to bind between two protofilaments and sense the specific nucleotide state of both flanking β-tubulins. Two talks focused on microtubule nucleation. Garrett Greenan (Ron Vale and David Agard laboratories, University of California, San Francisco) presented electron cryotomography reconstructions of centrioles from Drosophila and mammalian cell lines, which contain doublet and triplet microtubules, respectively. Although their overall ninefold symmetrical architecture is conserved, the reconstructions showed that in the absence of the C-tubule, Drosophila centriole doublets are connected via an A/A-linker, distinct from the A/C-linker seen in mammalian centrioles in both position and structure. Greenan postulated that this difference in architecture maintains the ability of the Drosophila centriole to recruit pericentriolar material and nucleate microtubules. Jan Brugués (Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany) examined what sets the upper size limit in spindles by measuring microtubule nucleation. Through a combination of laser ablation to measure minus ends with depletion experiments and mathematical modeling, Brugués presented evidence that the amount of active nucleators sets the size and mass of spindles through microtubulestimulated microtubule nucleation. The session then switched gears to microtubule-based motors. Stephen Norris (Ohi and Zanic laboratories, Vanderbilt University) focused on the microtubule minus end, specifically the role of kinesin-14 (HSET/KIFC1 in humans) in focusing supernumerary centrosomes to the two poles. Using single-molecule fluorescence based assays, he showed that soluble …