Microtubules structure

Maaloum M, Chretien D, Karsenti E and FIdrber J K FI 1994 Approaching microtubule structure with the scanning tunnelling microscope (STM) J. Ceii Sc/. 107 part II 3127... 

Epothilones A, B and E (4,5 and 6) (Fig. 2) are representative members of a new class of bacterially derived natural products which exhibit potent biological activity. Isolated by Hofle and coworkers [6] from a soil sample collected near the Zambesi river, the compounds have provided a great deal of excitement in the scientific community due to their potent cytotoxicity against a number of multiple drug-resistant tumor cell lines and because of the mechanism by which they exert this effect. Like Taxol [7], the epothilones promote the combination of a- and 3-tubulin subunits and stabilize the resulting microtubule structures. This mode of action inhibits the cell division process and is, therefore, an attractive strategy for cancer chemotherapy [7,8]. 

The polymer self-assembly theory of Oosawa and Kasai (1962) provides valuable insights into the nature of the nucleation process. The polymerization nucleus is considered to form by the accretion of protomers, but the process is highly cooperative and unfavorable. Indeed, this is strongly suggested by the observation that thousands of actin or tubulin protomers are found in F-actin and microtubule structures if nucleation of self-assembly were readily accomplished and highly favorable, the consequence would be that many more fibers of shorter polymer length would be observed. The Oosawa kinetic theory for nucleation permits one to obtain information about the size of the polymerization nucleus if two basic assumptions can be satisfied in the experimental system. First, the rate of nuclei formation is assumed to be proportional to the loth power of the protomer concentration with io representing the number of protomers required to create the nucleus. Second, the treat-... 

The principal cytoskeletal proteins in non-muscle cells are actin, tubulin, and the components of intermediate filaments. Actin can exist either as monomers ( G-actin ) or polymerized into 70 A diameter double filament ( F-actin ). Polymerized actin usually is localized at the margins of the cells, linked by other proteins to the cell membrane. In contrast, tubulin forms hollow filaments, approximately 250 A in diameter, that are distributed within a cell in association, generally, with cell organelles. Stabilized microtubule structures are found in the flagella and cilia of eucaryotic cells however, in other instances - examples being the mitotic apparatus and the cytoskeletal elements arising in directed cell locomotion - the microtubules are temporal entities. Intermediate filaments, which are composed of keratin-like proteins, are approximately 100 A thick and form stable structural elements that impart rigidity, for example, to nerve axons and epithelial cells. 

Amos LA and Lowe J (1999) How Taxol stabilizes microtubule structure. Chem Biol 6, R65-R69. 

Meurer-Grob, P., Kasparian, J., and Wade, R. H. (2001). Microtubule structure at improved resolution. Biochemistry 40, 8000-8008. 

Effect The mechanisms of action for aluminum toxicity is not known. Aluminum has a number of subcellular effects, such as affecting cation protein interactions or microtubule structure and effects on cellular signaling mechanisms, which can be observed in vitro. Further information would be useful in indicating whether these subcellular effects lead to disease processes. Studies on the mechanism of action of aluminum may lead to biochemical tests that can be used in the early identification of aluminum toxicity. 

The modification of the microtubule structure should come from the perturbation of the interprotofilament contacts, which allows the accommodation of extra protofilaments in the microtubule lattice. The experimental fact that taxane binding modifies the interprotofilament contacts rapidly lead to the conclusion that the taxane binding site in microtubules was located in the interprotofilament space [18, 19]. 

Tubulin-binding agents prepared by Pinney (4) consisting of dihydronaphthalene derivatives, (IV), exhibited potent tumor cell cytotoxicity by inhibiting the polymerization of a,(3-tubulin heterodimers into the microtubule structures and were used in the treatment of proliferation diseases. 

In 2001, several articles revealed a microtubule structure with improved resolu-tion. ° In the refined tubulin structure, the binding pocket of paclitaxel was modified shghtly. ° These structures will provide a good starting point in the construction of the pharmacophores of paclitaxel and other antitubulin dmgs. 

Keywords Tau Tauopathy Alzheimer s disease Frontotemporal dementia Parkinsonism Exon Microtubule Structural Protein Phosphorylation... 

AvUa J. Microtubule Proteins. 1989. CRC Press, Boca Raton, FL. This book covers various aspects of microtubule and microtubule-associated proteins. In addition, detailed descriptions of the relationship between microtubule structure and functions, microtubule proteins, it elaborates microtubule dynamics, and microtubule poisons. 

Figure 34.21. Microtubule Structure. Schematic views of the helical structure of a microtubule, a-tubulin is shown in dark red and P-tubulin in light red. (A) Top view. (B) Side view.

The synapse is known to be in indirect yet intimate contact with the microtubule structure of the neuron.) This model has the immediate advantage, as Hameroff points out, of increasing the potential effective complexity and storage capacity of the brain by about seven orders of magnitude,... 

R. H. Wade and A. A. Hyman Microtubule structure and dynamics. Current Opinion in Cell Biology 9, 12 (1997). 

Finally, 80 proteins localized to an abnormal intranuclear microtubule structure upon LMB treatment, while others simply occupied nucleus or nucleolus. Crml-dependent dynamic interchange of proteins between the nucleus and the microtubules may regulate microtubule organization during the cell cycle in fission yeast. Further analysis of individual proteins will reveal the involvement of Crml in the process for microtubule assembly and disassembly. 

Active only against dermatophytes (orally, not topically) by depositing in newly formed keratin and disrupting microtubule structure. 

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