Abstract
Growing evidence continues to point toward the critical role of beta tubulin isotypes in regulating some intracellular functions. Changes that were observed in the microtubules’ intrinsic dynamics, the way they interact with some chemotherapeutic agents, or differences on translocation specifications of some molecular motors along microtubules, were associated to their structural uniqueness in terms of beta tubulin isotype distributions. These findings suggest that the effects of microtubule associated proteins (MAPs) may also vary on structurally different microtubules. Among different microtubule associated proteins, Tau proteins, which are known as neuronal MAPs, bind to beta tubulin, stabilize microtubules, and consequently promote their polymerizations.In this study, in a set of well controlled experiments, the direct effect of Tau proteins on the polymerization of two structurally different microtubules, porcine brain and breast cancer (MCF7), were tested and compared. Remarkably, we found that in contrast with the promoted effect of Tau proteins on brain microtubules’ polymerization, MCF7 expressed a demoted polymerization while interacting with Tau proteins. This finding can potentially be a novel insight into the mechanism of drug resistance in some breast cancer cells.It has been reported that microtubules show destabilizing behavior in some MCF7 cells with overexpression of Tau protein when treated with a microtubules’ stabilizing agent, Taxol. This behavior has been classified by others as drug resistance, but it may instead be potentially caused by a competition between the destabilizing effect of the Tau protein and the stabilizing effect of the drug on MCF7 microtubules. Also, we quantified the polarization coefficient of MCF7 microtubules in the presence and absence of Tau proteins by the electro-orientation method and compared the values. The two significantly different values obtained can possibly be one factor considered to explain the effect of Tau proteins on the polymerization of MCF7 microtubules.
Highlights
Microtubules, one of the intra-cellular biofilaments, play a significant role in many cell functions including cellular morphology, cell division, and cellular transportation
The longer average length of Tau-porcine microtubules confirmed that the polymerization of porcine brain tubulin was promoted due to the interactions with Tau proteins – an outcome which is consistent with previously reported results [9,10,11,12]
The results of our studies and others indicate that the differences which exist in the composition of microtubules in terms of distribution of beta tubulin isotypes, may alter both their biomechanical specifications, as well as functions of some molecular motors along them [25,26,27,28,29,30,31,32,33,34,35]
Summary
Microtubules, one of the intra-cellular biofilaments, play a significant role in many cell functions including cellular morphology, cell division, and cellular transportation. These biofilaments that are composed of alpha and beta tubulin exhibit dynamic instability, an unstable behavior that they express between two phases of growth and shortening during their polymerization [1,2,3,4,5]. Other evidence indicates that the Tau protein regulates the interaction of some molecular motors and their transport along microtubules [11] These dual interactions with microtubules and molecular motors, place Tau protein at the focus of many investigations, as their abnormal functionalities may lead to neurodegeneration diseases, such as Alzheimer and Down Syndrome [12]
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