Microtubular polymerization, effect

Taxanes (paclitaxel, docetaxel) are derivatives of yew tree bark (Taxus brevifolia). They stabilize microtubules in the polymerized state leading to nonfunctional microtubular bundles in the cell. Inhibition occurs during G2- and M-phases. Taxanes are also radiosensitizers. Unwanted effects include bone marrow suppression and cumulative neurotoxicity. 

Compounds 338 and 339 have been shown to disrupt microfilament organization and exert profound effects on the morphology of nonmuscle cells without affecting the organization of the microtubular system [256]. Compound 338 was found to affect the polymerization of pure actin in a manner consistent with the formation of a 1 1 complex with G-actin. This phenomenon affected different components of the actin-based cytoskeleton [256]. Comparison to cytochalasin showed 338 to be an order... 

Another type of controlled radical polymerization employs a reversible termination with a nitroxide compound [21]. Rosenfeld et al. [22] reported details of the nitroxide-mediated radical polymerization of styrene and butyl acrylate at 140 °C in a 2.9 m tubular micro-reactor with an inner diameter of 900 gm. Whereas, for the low-heat-producing monomer, styrene, the differences between a batch process and the microtubular reaction were small, in the case of butyl acrylate the difference was high. This situation, which may have been due to the Trommsdorff effect in the batch reaction (Figure 14.11), indicated that the polymerization was no longer under control. By contrast, no such effect was observed in the tubular micro-reactor, and the degree of conversion remained quite low under the applied conditions. 

The force which propels secretory granules along the microtubules is less clear. It is known that the micro tubular system exists in at least two states the fully polymerized form represented by intact microtubules, and the disintegrated form represented by a pool of depolymer-ized globular proteins (tubulin) in the cytoplasm. In order for microtubules to function properly, a dynamic state of equilibrium must exist between the fully-formed tubules and the tubule constituent pool. Thus, colchicine and other antimitotic agents bind to specific sites on the microtubular subunits. It has been proposed that they exert their effect by inactivating the free subunits and thereby shift the equilibrium between the associated and dissociated states of the microtubules so that eventually no intact microtubules remain and secretion is inhibited. Similarly, stabilization of microtubules in the polymerized form with D2O also inhibits cellular secretion of insulin. From this, one can hypothesize that if the secretory vesicles were somehow attached to the microtubules, possibly by way of microfilaments, a constant cycle of depolymerization near the cell periphery, with a repolymerization at the central area of the cell, would advance the secretory vesicle from the cell center to the cell web. In addition, if tubulin actually contains an actin-like contractile protein, then this contractile property may well contribute to the intracellular movement of secretory materials. 

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