Chemotaxis Microtubules

Vinca alkaloids (vincristine, vinblastine, vindesine) are derived from the periwinkle plant (Vinca rosea), they bind to tubulin and inhibit its polymerization into microtubules and spindle formation, thus producing metaphase arrest. They are cell cycle specific and interfere also with other cellular activities that involve microtubules, such as leukocyte phagocytosis, chemotaxis, and axonal transport in neurons. Vincristine is mainly neurotoxic and mildly hematotoxic, vinblastine is myelosuppressive with veiy low neurotoxicity whereas vindesine has both, moderate myelotoxicity and neurotoxicity. 

Tubulin is a major component of the cellular cytoskele-ton. Tubulin polymers (microtubules) are important for cell division (mitotic spindle) and the chemotaxis and phagocytosis of neutrophils. Prevention of tubulin polymerisation by colchicine accounts for the therapeutic effects of this drug in acute gouty arthritis and its anti-mitotic effects. 

Vinca alkaloids are derived from the Madagascar periwinkle plant, Catharanthus roseus. The main alkaloids are vincristine, vinblastine and vindesine. Vinca alkaloids are cell-cycle-specific agents and block cells in mitosis. This cellular activity is due to their ability to bind specifically to tubulin and to block the ability of the protein to polymerize into microtubules. This prevents spindle formation in mitosing cells and causes arrest at metaphase. Vinca alkaloids also inhibit other cellular activities that involve microtubules, such as leukocyte phagocytosis and chemotaxis as well as axonal transport in neurons. Side effects of the vinca alkaloids such as their neurotoxicity may be due to disruption of these functions. 

The role of microtubules in neutrophil function can be investigated using agents such as colchicine, colcemid, vinblastine and vincristine, which disrupt these structures. Stimulation of neutrophils with chemotactic agents causes a rapid and transient assembly of microtubules, but this assembly does not affect chemotaxis. Similarly, cytoplasts (neutrophils devoid of nu-... 

Cytoskeleton is defined as the sum of the various filamentous proteins of eukaryotic cells that remain after the cells are extracted with a mild detergent. The cytoskeleton includes actin filaments, two-stranded helical polymers, which form the microfilaments and the actin-binding proteins. Other components are microtubules and intermediate filaments. The cytoskeleton has not only a role in maintaining the shape of cells, it is also actively engaged in cell division, in the organisation and the dynamic movement of ceD organelles and in the movement of cells in chemotaxis. 

Although there is evidence that both the actin and microtubule cytoskeletal systems contribute to amoeboid chemotaxis, the evidence is strongest for the importance of the actin cytoskeleton. Drugs that inhibit the actin cytoskeleton, such as cytochalasins, have dramatic effects on chemotaxis, at least in part due to an inhibition of cell motility [202]. Assays of actin localization and polymerization indicate that chemoattractant stimulation has strong effects on the actin cytoskeleton... 

On the other hand, microtubule-depolymerizing agents such as nocodazole have generated less consistent results [202], Nevertheless, overexpression of a tubulin deacetylase affects chemotactic cell movement, indicating possible contributions of microtubules to chemotaxis [98], In addition, microtubules may contribute to the regulation of cell polarity and adhesion stability through interactions with the actin cytoskeleton. 

As noted previously, the evidence for the contribution of microtubules to amoeboid cell motility and chemotaxis is mixed [242]. The microtubule organizing center has been reported to be localized to either the front or rear side of the nucleus, depending upon the cell type [167, 187, 188]. Alterations in microtubules can affect fibroblast lamellipod extension and motility [150], but in some assays, chemotactic responses may be unaffected [202]. Alterations in acetylation enhance chemotactic ability [98]. Microtubules have been proposed to alter the stability of adhesion sites, enhancing their disassembly [II9]. In sum, microtubules are likely to be permissive for amoeboid motility and chemotaxis, and respond to polarization of the cell generated by the actin system with polarization of the microtubule system. This may in turn stabilize cell polarity and enhance overall chemotactic efficiency. In the absence of a strong external stimulus, or in cases in which autocrine secretion influences cell polarization, the microtubule apparatus may provide critical signals for cell polarity [164]. 

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