Microtubule organizing complex

Centrosomes, also called the microtubule organizing centre, are protein complexes that contain two cen-trioles (ringlike structures) and y- tubulin. They serve as nucleation points for microtubular polymerization and constrain the lattice structure of a microtubule to 13 protofilaments. They are responsible for organizing the mitotic spindle during mitosis. 

Microtubule assembly in cells differs in some ways from assembly in vitro. In cells, nucleation of microtubules requires a third type of tubulin, which is called y-tubulin, that functions in concert with other proteins in the form of a y-tubulin ring complex. In most animal cells, the y-tubuIin ring complex is located at the pericentriolar region of the microtubule organizing center (or centrosome) where it nucleates microtubule assembly at the minus ends (7). The y-tubulin does not become incorporated into the microtubule, but rather it only localizes to the minus ends. Assembly of tubulin to form microtubules during the early stages of polymerization in vitro can be considered a pseudo first-order reaction. A steady state is eventually attained in which both the soluble tubulin concentration and the microtubule polymer mass attain stable plateaus (8). The critical concentration at apparent equilibrium (actually a steady state, see below) is the concentration of soluble tubulin in apparent equilibrium with the microtubule polymers. 

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Wiese C, Zheng Y. 1999. Gamma-tubulin complexes and their interaction with microtubule-organizing centers. Curr. Opin. Struct. Biol. 9 250-59... 

Turner, G.R. Tartakoff, A.M. (1989). The response of the Golgi complex to microtubule alterations The roles of metabolic energy and membrane traffic in Golgi complex organization. J. Cell Biol. 109,2081-2088. 

The steps in the development of anticancer drugs from (marine) organisms are schematically shown in Fig. 7. The most important step in the selection process is initial mass screening. The screening methods can either be simple, such as tumor cell line or enzymatic (e.g., topoisomerase inhibition, microtubule as-sembly/dissassembly) tests, or more complex, such as an animal tumor in vivo. 

Further refinement of the electron crystallographic structure of tubulin-paclitaxel at 3.5A resolution delivered a similar result. Nevertheless, the T-Taxol model has not been completely accepted as the actual bioactive conformation [78], It is evident that the low 3.5-3.7A resolution of the complex limits the precision of the resulting model. In addition, the Zn2+-stabilized tubulin preparation employed in the electron crystallographic study involves antiparallel protofilaments organized in sheets, which strongly differ from genuine microtubules. Consequently, concern has been expressed that the sheets may not be representative of cellular microtubules and that sheet-bound paclitaxel geometry may differ from its bioactive form in microtubules. 

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