n from earlier experiments with taxol on primary cytotoxic T-lymphocytes that microtubule dynamics is not required for the immunologically functional orientation of the centrosome in T cells. These new and previously published results of experiments in which microtubule dynamics was directly modulated with inhibitors are at odds with the speculations that microtubule dynamics as such may be involved in T cell polarization, which speculations find support only in T-cell signaling studies. The results of the 16522807 direct microtubule dynamics inhibition also argue against drawing analogy between T-cell polarization and microtubule rearrangements in mitosis. In its insensitivity to abrogation of microtubule dynamics by taxol, polarization of T-cell centrosomes to the target, rather, parallels other types of microtubule rearrangements characteristic of leukocytes: during initiation of migration in neutrophils and during retraction into the uropod in motile T cells. Our experiments reveal a subtler effect of micromolar taxol but not of nanomolar nocodazole on the centrosome positioning in polarized T cells. Micromolar taxol promoted peripheral localization of T-cell centrosomes within the contact zone of T cells with the target surface. It should be emphasized that these centrosomes are still at the interface with the target and are in this sense polarized functionally. At the same time this effect appears potentially very significant in the emerging framework that recognizes T cells as sending spatially differentiated signals to Conclusions and outlook T-Cell Polarity the target and ��bystander��cells. It is conceivable and merits experimental investigation that the peripheral-synaptic centrosome localization results in spatially mixed signaling, in which case its buy Chlorphenoxamine representation in the cell population will be important for the overall degree of signal segregation. The observed contrast between the control and taxol-treated cell populations indicates that the centrosome position may normally be under tighter control than merely ensuring its proximity to the target. At the same time, absence of the centrosome displacement from the synapse center 22754608 in cells treated with nanomolar nocodazole indicates that the more precise positioning of the centrosome within the synapse does not require microtubule dynamics either. The results of our computational modeling demonstrate that the effect of taxol on centrosome orientation can be rigorously explained by lengthening of the stabilized microtubules, which is specific to the micromolar taxol. 
Our computational modeling approach assumes static microtubule length. Thus, even the secondary effect of taxol on centrosome positioning in T cell can be explained without invoking suppression of the microtubule dynamics as such. This rigorous theoretical result lends further support to the notion that microtubule dynamics per se are not involved in the functional centrosome polarization in activated T cells, not even in the finer aspects of the centrosome positioning. Another effect of taxol on microtubules is promotion of acetylation. The present biomechanical model deals only with cell-scale structural properties of the microtubules, such as their number and length. It cannot be used to study the potential effect of a biochemical modification such as the acetylation. Therefore, even though our model rigorously explains the peripheral centrosome localization as being a consequence of microtubule elongation, it does not ri
