Cytochalasin
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Cytochalasins are fungal metabolites that have the ability to bind to actin filaments and block polymerization and the elongation of actin. As a result of the inhibition of actin polymerization, cytochalasins can change cellular morphology, inhibit cellular processes such as cell division, and even cause cells to undergo apoptosis (Haidle and Myers, 2004)[1]. Cytochalasins have the ability to permeate cell membranes, prevent cellular translocation and cause cells to enucleate (Cooper, 1987)[2]. Cytochalasins can also have an effect on other aspects on biological processes unrelated to actin polymerization. For example, cytochalasin A and cytochalasin B can also inhibit the transport of monosaccharides across the cell membrane (Cooper, 1987), cytochalasin H has been found to regulate plant growth (Cox et al., 1983)[3], cytochalasin D inhibits protein synthesis (Ornelles et al., 1986)[4] and cytochalasin E prevents angiogenesis (Udagawa et al., 2000)[5].
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[edit] Binding to Actin Filaments
Cytochalasins are known to bind to the barbed, fast growing plus ends of microfilaments, which then blocks both the assembly and disassembly of individual actin monomers from the bound end. Once bound, cytochalasin essentially caps the end of the new actin filament. One cytochalasin will bind to one actin filament (Cooper, 1987). Studies done with Cytochalasin D (CD) have found that the formation of CD-actin dimers, contain ATP bound actin (Goddette and Frieden, 1986)[6]. These CD-actin dimers are reduced to CD-actin monomers as a result of ATP hydrolysis. The resulting CD-actin monomer can bind ATP-actin monomer to reform the CD-actin dimer (Cooper, 1987). CD is very effective; only low concentrations (0.2 μM) are needed to prevent membrane ruffling and disrupt treadmilling (Yahara et al., 1982). Yahara et al. (1982)[7] found that higher concentrations (2-20 μM) of CD were needed to remove stress fibers. Yahara et al. (1982) analyzed the effects of many different cytochalasins had on actin filaments.
[edit] Uses and Applications of Cytochalasins
Actin microfilaments have been widely studied using cytochalasins. Due to their chemical nature, cytochalasins can help researchers understand the importance of actin in various biological processes. The use of cytochalasins have allowed researchers to better understand actin polymerization, cell motility, ruffling, cell division, contraction, and cell stiffness. The use of cytochalasins has been so important to understanding cytoskeletal movement and many other biological processes, researchers have created two synthetic cytochalasins (Haidle and Myers, 2004).[8]
[edit] References
- ^ Haidle, Andrew and Myers, Andrew (2004). An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B. Proc. Natl. Acad. Sci. USA 101, 12048-12053.
- ^ Cooper, John A. (1987). Effects of Cytochalasin and Phalloidin on Actin. J. Cell Biol. 105, 1473-1478.
- ^ Cox, R. H., Cutler, H. G., Hurd, R. E. & Cole, R. J. (1983) J. Agric. Food Chem. 31, 405–408.
- ^ Ornelles et al. (1986) Cytochalasin releases mRNA from the cytoskeletal framework and inhibits protein synthesis. Mol. Cell Biol. 6, 1650-1662.
- ^ Udagawa, T., Yuan, J., Panigrahy, D., Chang, Y.-H., Shah, J. & D’Amato, R. J. (2000) J. Pharmacol. Exp. Ther. 294, 421–427.
- ^ Goddette and Frieden (1987) Actin polymerization: the mechanism of action of cytochalasin D. J. Biol. Chem. 261, 15974-15980.
- ^ Yahara et al. (1982). Correlation between Effects of 24 Different Cytochalasins on Cellular Structures and Cellular Events and Those on Actin In Vitro. J. Cell Biol. 92, 69-78.
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