Microtubule elongation

As noted earlier, microtubule elongation has been characterized largely with respect to the involvement of guanine nucleotides and the modes of drug inhibition of microtubule formation. There have also been a number of important studies on the influence of microtubule-associated proteins and solution variables on the kinetics and thermodynamics of microtubule self-assembly. Of these, the characterization of the so-called mitotic spindle poisons has been particularly complex because of the variety of agents and the diversity of systems studied. For this reason, we shall concentrate on the other factors affecting the elongation process. 

The first comparison of the kinetics of E-site GTP hydrolysis and microtubule elongation was carried out by MacNeal and Purich (1978a). Their results indicated that the hydrolysis and elongation reactions were coupled because there was only a very slight lag in the hydrolytic process at the concentrations of microtubule protein employed. These data do not distinguish between two mechanistic alternatives ... 

Other Factors Affecting Microtubule Elongation Reactions... 

Summary of the Kinetic and Equilibrium Constants Characterizing Microtubule Elongation from Chlamydomonas Flagellar Axonemes"... 

Figure 5.15. Turbidity-time curve for microtubule assembly.The diagram illustrates the turbidity-time changes that occur during microtubule assembly. Initially during the turbidity lag phase, tubulin monomers form rings of tubulin subunits that cause microtubule elongation during the growth phase.

Figure 3 A typical microtubule assembly reaction is initiated by warming a solution of ice-cold tubulin dimers to 37°C in the presence of GTP. Tubulin dimers (adjacent white and gray circles) slowly form nucleating seeds (heptameric tubulin aggregate), which catalyze a rapid phase of microtubule elongation (growing microtubule) enroute to a steady state condition of microtubule formation and destruction. The assembly reaction is monitored by measuring the change in absorbance at 350 nm. In vitro incubation of microtubules with 2,5-HD or in vivo exposure of animals to 2,5-HD followed by tubulin purification yields pyrrolylated tubulin with altered assembly behavior. 2,5-HD-modified tubulin quickly forms numerous seeds, resulting in more rapid assembly into greater numbers of shorter microtubules compared to the control.

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