Cytochalasin and Actin

A direct link between cytochalasin and actin was provided by the demonstration that cytochalasin decreases the viscosity of actin filaments purified from muscle (50). This experiment led to two important conclusions. First, cytochalasin interacts directly with actin. Second, an interaction of cytochalasin with actin or actin-like proteins in vivo could account for the ability of cytochalasin to inhibit various forms of cell motility and contraction (50). Thus, actin was shown to be the molecular target of cytochalasin and implicated as a critical component of the microfilaments involved in cytochalasin-sensitive processes, including contraction of the cleavage furrow at cytokinesis. 

Using actin filaments purified from muscle, cytochalasin was shown to decrease the viscosity of actin in solution. This experiment, which established a direct link between cytochalasin and actin, led to two important conclusions. First, cytochalasin interacts directly with actin. Second, an interaction of... 

Recently, in 2008, the exact binding situation between cytochalasin and actin was clarified, as Trybus et al. achieved the crystallization of cytochalasin D (1091) in complex with actin (Fig. 14.4) (711). 

The cy tochalasins A, B, C, D, E, and H are found in various species of mould. Mainly cytochalasin B and D are used as experimental tools. Cytochalasin D is 10 times more potent, acting at concentrations between 2 and 35 nM in cell-free systems. Cy tochalasins bind to the barbed end of F-actin and block the addition as well as dissociation of G-actin at that end. At micromolar concentrations, cytochalasin D can bind to G-actin and actin dimers and thus block additional polymerization. When applied to cultured cells, micromolar concentrations of cytochalasins remove stress fibres and other F-actin structures. 

Cytokinesis (cell division) in animal cells involves the progressive formation in telophase of a furrow between the two daughter cells in the equator of the mitotic spindle. Immunofluorescent staining of the cortical cytoplasm at the site of the contraction ring reveals an abundance of actin as well as myosin, a-actinin, and filamin (Fishkind and Wang, 1995). Cytokinesis is highly sensitive to actin-myosin inhibitors such as cytochalasin and phalloidin. 

Flanagan, M.D., and S. Lin. 1980. Cytochalasins block actin filament elongation by binding to high affinity sites associated with F-actin. J Biol Chem 255 835. 

Cooper JA (1987) Effects of cytochalasin and phalloidin on actin. In J. Cell Biol. 105 1473-8... 

Cooper, (.A. (1987) Effects of cytochalasins and phalloidin on actin. /. Ceil Biol., 105,1473-1478. 

Hirose, K., Izawa, Y, Koyama, K., Natori, S., lida, K., Yahara, I., Shimaoka, S., and Maruyama, K. (1990) The effects of new cytochalasins from Phomopsis sp. and the derivatives on cellular structure and actin polymerization. Chem. Pharm. Bull, 38, 971-974. 

Cytochalasins B and D are used as tools to study F-actin. Cytochalasins bind to the barbed end of F-actin and block the addition as well as dissociation of G-actin at that end. When applied to cultured cells micromolar concentrations of cytochalasins remove stress fibres and other F-actin structures. 

Nevertheless, there are reports on enhancement of ocular drug absorption by bile salts [33], surfactants [200], and chelators [149], Newton et al. [35] demonstrated that Azone, an enhancer widely tested in transdermal drug delivery [201], increased the ocular absorption of cyclosporine, an immunosuppressant, by a factor of 3, thereby prolonging the survival of a corneal allograft. In 1986, Lee et al. [34] reported that 10 pg/mL cytochalasin B, an agent capable of condensing the actin microfilaments, increased the aqueous humor and iris-ciliary body concentrations of topically applied inulin (5 kDa) by about 70% and 700%, respectively, in the albino rabbit. 

Bengtsson, T., Dahlgren, C., Stendahl, 0., Andersson, T. (1991). Actin assembly and regulation of neutrophil function Effects of cytochalasin B and tetracaine on chemo-tactic peptide-induced 02" production and degranulation. J. Leuk. Biol. 49,236-44. 

Forscher P and Smith SJ [1988] Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone. J Cell Biol 107 1505-1516... 

Sampath P and Pollard TD [1991] Effects of cytochalasin, phalloidin and pH on the elongation of actin. Biochemistry 30 1973-1980... 

Because of the strict requirement for actin, the most commonly used inhibitors of macropinocytosis are the cytochalasins, especially cytochalasin D or toxin C. These substances also block phagocytosis and intracellular trafficking along actin filaments. Therefore, the results from these experiments are described in the trafficking section Actin Dependence on Liposome Uptake. ... 

The involvement of the actin cytoskeleton in liposome endocytosis is studied by using cytochalasins, latrunculin, or toxin C2 to polymerize actin filaments. For a review on actin assembly and endocytosis, see Ref. (135). 

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