An experimental and computational study of effects of microtubule stabilization on T-cell polarity.
An experimental and computational study of effects of microtubule stabilization on T-cell polarity.
复制标题
微管稳定对T细胞极性的影响的实验和计算研究。
DOI：
10.1371/journal.pone.0003861
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Maly, Ivan V.
中科院分区：
文献类型：
--
作者：
Baratt, Arie;Arkhipov, Sergey N.;Maly, Ivan V.
T-杀伤细胞通过将中心体定位在与靶细胞的界面（免疫突触）附近，精确地消除感染细胞和癌细胞。中心体定位的机制仍然存在争议，特别是微管动力学在it. We的作用重新研究的问题，在Jurkat细胞的实验模型提出了一个T细胞受体结合的人工基板，它允许控制刺激和可重复的测量。1 μM紫杉醇和100 nM诺考达唑都不能抑制中心体在仿生底物“突触”上的定位。与此同时，在微摩尔紫杉醇，而不是在纳摩尔诺考达唑的中心体采用了一个独特的周边，而不是正常的中心位置内的突触。这种效应在一个计算能量最小化模型中重现，该模型假设没有微管动力学，但只有紫杉醇诱导的微管长度增加。总之，实验和计算结果表明，微管动力学对于中心体定位并不是必不可少的，但微管阵列在缀合T细胞变形体内的匹配是一个主要因素。用经过充分研究的药物调节T细胞中心体位置并通过计算机模拟预测其效果的可能性对于设计抗癌和抗病毒疗法似乎很有吸引力。
T-killer cells eliminate infected and cancerous cells with precision by positioning their centrosome near the interface (immunological synapse) with the target cell. The mechanism of centrosome positioning has remained controversial, in particular the role of microtubule dynamics in it. We re-examined the issue in the experimental model of Jurkat cells presented with a T cell receptor-binding artificial substrate, which permits controlled stimulation and reproducible measurements. Neither 1-µM taxol nor 100-nM nocodazole inhibited the centrosome positioning at the “synapse” with the biomimetic substrate. At the same time, in micromolar taxol but not in nanomolar nocodazole the centrosome adopted a distinct peripheral rather than the normally central position within the synapse. This effect was reproduced in a computational energy-minimization model that assumed no microtubule dynamics, but only a taxol-induced increase in the length of the microtubules. Together, the experimental and computational results indicate that microtubule dynamics are not essential for the centrosome positioning, but that the fit of the microtubule array in the deformed body of the conjugated T cell is a major factor. The possibility of modulating the T-cell centrosome position with well-studied drugs and of predicting their effects in silico appears attractive for designing anti-cancer and antiviral therapies.
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影响因子：
2
作者：
Howard, J
通讯作者：
Howard, J
影响因子：
--
作者：
KNOX, JD;MITCHEL, REJ;BROWN, DL
通讯作者：
BROWN, DL
影响因子：
2
作者：
Arkhipov, Sergey N.;Maly, Ivan V.
通讯作者：
Maly, Ivan V.
影响因子：
4.3
作者：
BYKOVSKAJA, SN;RYTENKO, AN;BYKOVSKY, AF
通讯作者：
BYKOVSKY, AF
影响因子：
3.3
作者：
Eddy, RJ;Pierini, LM;Maxfield, FR
通讯作者：
Maxfield, FR