The taccalonolides and paclitaxel cause distinct effects on microtubule dynamics and aster formation.
The taccalonolides and paclitaxel cause distinct effects on microtubule dynamics and aster formation.
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DOI：
10.1186/1476-4598-13-41
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发表时间：
2014-02-28
期刊：
影响因子：
37.3
通讯作者：
Mooberry SL
中科院分区：
文献类型：
--
作者：
Risinger AL;Riffle SM;Lopus M;Jordan MA;Wilson L;Mooberry SL
微管稳定剂抑制微管动力学，并在最低的抗增殖浓度下破坏有丝分裂纺锤体的功能，导致有丝分裂停滞和细胞凋亡。在稍高的浓度下，这些试剂会导致由不同的微管稳定剂引发的具有不同形态的多个有丝分裂紫苑的形成。我们测试了这样的假设：两类微管稳定药物（紫杉烷类和他卡酮内酯）会导致不同的紫苑结构的形成，部分原因是对微管动力学的不同影响。紫杉醇和他卡洛内酯抑制了由纯化的微管蛋白以及活细胞中形成的微管的动力学。两种药物均抑制微管动态不稳定性，其中他卡酮内酯对微管突变具有更显着的抑制作用，表明它们比紫杉醇更有效地稳定微管的正端。活细胞显微镜也用于评估药物处理后紫苑的形成和分解。虽然每种药物对初始形成具有相似的影响，但在紫苑分辨率方面观察到显着差异。紫杉醇诱导的紫苑通常会随着时间的推移而聚结，导致更少、更大的紫苑，而在塔卡酮内酯存在下形成后，大量致密的紫苑会持续存在。我们得出的结论是，微管两端对灾难的抵抗力增加可能在观察到的他卡酮内酯诱导的紫苑在有丝分裂期间无法聚结的过程中发挥了作用，从而导致暴露于这些试剂后观察到的独特形态。
Microtubule stabilizers suppress microtubule dynamics and, at the lowest antiproliferative concentrations, disrupt the function of mitotic spindles, leading to mitotic arrest and apoptosis. At slightly higher concentrations, these agents cause the formation of multiple mitotic asters with distinct morphologies elicited by different microtubule stabilizers. We tested the hypothesis that two classes of microtubule stabilizing drugs, the taxanes and the taccalonolides, cause the formation of distinct aster structures due, in part, to differential effects on microtubule dynamics. Paclitaxel and the taccalonolides suppressed the dynamics of microtubules formed from purified tubulin as well as in live cells. Both agents suppressed microtubule dynamic instability, with the taccalonolides having a more pronounced inhibition of microtubule catastrophe, suggesting that they stabilize the plus ends of microtubules more effectively than paclitaxel. Live cell microscopy was also used to evaluate the formation and resolution of asters after drug treatment. While each drug had similar effects on initial formation, substantial differences were observed in aster resolution. Paclitaxel-induced asters often coalesced over time resulting in fewer, larger asters whereas numerous compact asters persisted once they were formed in the presence of the taccalonolides. We conclude that the increased resistance of microtubule plus ends to catastrophe may play a role in the observed inability of taccalonolide-induced asters to coalesce during mitosis, giving rise to the distinct morphologies observed after exposure to these agents.
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影响因子：
11.2
作者：
Risinger AL;Jackson EM;Polin LA;Helms GL;LeBoeuf DA;Joe PA;Hopper-Borge E;Ludueña RF;Kruh GD;Mooberry SL
通讯作者：
Mooberry SL
影响因子：
11.2
作者：
Orth JD;Kohler RH;Foijer F;Sorger PK;Weissleder R;Mitchison TJ
通讯作者：
Mitchison TJ
影响因子：
56.9
作者：
Quintyne, NJ;Reing, JE;Saunders, WS
通讯作者：
Saunders, WS
影响因子：
--
作者：
Hornick, Jessica E.;Bader, Jason R.;Tribble, Emily K.;Trimble, Kayleigh;Breunig, J. Scott;Halpin, Elizabeth S.;Vaughan, Kevin T.;Hinchcliffe, Edward H.
通讯作者：
Hinchcliffe, Edward H.
DOI：
10.1073/pnas.90.20.9552
发表时间：
1993-10-15
影响因子：
11.1
作者：
JORDAN, MA;TOSO, RJ;WILSON, L
通讯作者：
WILSON, L