14% of untreated cells had their centrosomes at the periphery of the area of the cell’s contact with the substrate. The same proximity criterion was used to classify the cell as having a peripheral location of the centrosome as for determining the polarization to the substrate: the centrosome’s location was called peripheral if it was within 2 mm from the outline of the cell-substrate contact area. In contrast to the small fraction of untreated cells with the peripheral centrosome location, most cells treated with taxol exhibited the peripheral location of the centrosome 40 min after contacting the substrate. It is important to notice that the centrosomes that we call peripheral were still polarized to the substrate according to the proximity criterion, and that they were still positioned within the zone of the cell’s ��synapse��with the substrate. To our knowledge, this effect of taxol on the centrosome positioning in T cells has not been reported before. Reexamination of the published structure of a T-killer cell conjugated with a target cell after taxol treatment showed that it was visually consistent with our new finding. The taxol-induced shift of the typical orientation of the T-cell centrosome is potentially significant for the T-cell function. The simultaneous but differential secretion of immunological mediators in the direction of the target cell and ��bystander��cells could be modulated by the degree of proximity of the main secretory apparatus to the margin of the synaptic area. Firstly, the 20171952 taxol-induced perturbation suggests that the exact position of the centrosome within the synaptic area may normally be under cellular control. Secondly, this perturbation may have direct implications for the therapeutic use of taxol, which will be discussed below. To test whether the peripheral centrosome localization was a consequence of inhibiting microtubule dynamics, we determined the centrosome position in cells treated with another microtubule dynamics inhibitor, nocodazole at 100 nM. This treatment did not have any effect either on polarization of the centrosome to the substrate or on the proportion of cells with centrosomes at the periphery of the 
cell-substrate contact zone. From these results we conclude that the peripheral localization of the centrosome in the taxol-treated cells was likely caused by other effects of taxol than the inhibition of the microtubule dynamics as such. Although mechanisms of action of microtubule drugs are complicated, it is generally accepted that there is a significant difference between the action of micromolar taxol and nanomolar nocodazole. Micromolar taxol stabilizes microtubules by shifting the assembly-disassembly balance greatly in favor of assembly. In contrast, nanomolar nocodazole inhibits assembly as well as disassembly, without inducing dissolution of the entire microtubule cytoskeleton that is characteristic of micromolar nodocazole NU7441 web concentrations. In view of the established difference between taxol and nocodazole action, we were led to hypothesize that the induction of the peripheral polarized position of the centrosome in our experiments specifically by taxol could be due to lengthening of microtubules caused by the 15771452 assembly-promoting action specific to micromolar taxol and not to nanomolar nocodazole. There is no intuitive explanation, though, for how microtubule lengthening could cause the peripheral and at the same time polarized location of the centrosome. The model reproduces the t
