Actin-stress fibers

Ridley, A.J., Hall, A. (1992). The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70,389-399. 

However, 2 also affected the regulation of actin stress fiber formation [19]. Rho proteins are involved in the regulation of various cytoskeletal structures, and RhoB is believed to be one of the prime targets of FTase inhibitors. Rho B is apparently both geranylgeranylated and farnesylated [20, 21]. If cells were treated with 2, vesicular localization of Rho B was inhibited. Thus 2 may also inhibit the farnesylation of Rho B, thereby interfering with actin stress fiber formation [22]. 

Any of the cytoskeletal proteins that cross-link cytoskel-etal filaments into colinear arrays, such as the action of a-actinin in promoting the formation of actin stress fibers. Bundling proteins typically contain pairs of binding sites for attachment to cytoskeletal filaments. 

Seifert, G. J., Lawson, D., and Wiche, G. (1992). Immunolocalization of the intermediate filament-associated protein plectin at focal contacts and actin stress fibers. Eur. J. Cell Biol. 59, 138-147. 

In addition to Ras, a number of other proteins are known to be substrates for FTase (many of unknown identity or function, determined by 2-D gel shift experiments in the presence and absence of FTI) these may also play a part in determining relative susceptibility to FTase inhibition.46 In particular, RhoB, a farnesylated protein involved with the formation of actin stress fibers and cytoskeletal organization, has been implicated in the growth-inhibitory consequences of FTase inhibition.47,48 Another study using the FTI 19 found that growth inhibition in soft agar of a panel of human tumor cell lines correlated with the mutational status of the H-and N-Ras proteins, but not with K-Ras mutations.49 In this study also, cells with genetic defects in addition to ras were sensitive to FTase inhibition. 

The structural integrity of microfilaments has been shown to be necessary for signal transduction within osteoblasts. Examination of the effects of mechanical strain on the expression of major structural elements of the cytoskeleton indicated that the amount of tubulin decreased by 75% and the amount of vinculin, a major component of focal adhesion complexes, increased by about 250%. Immunofluorescence microscopy demonstrated that mechanical strain led to increased formation and thickening of actin stress fibers, with dissociation of the microtubules and a clear increase in levels of vinculin at the peripheral edges of the cell. This suggests that mechanical strain leads to a coordinated change in both the cytoskeleton and in ECM proteins that facilitate tighter adhesion of osteoblasts and their ECM. 

Abnormalities in the actin cytoskeleton, including decreased actin stress fibers and altered response to depolymerizing agents were also observed in Lowe patients (Suchy and Nussbaum, 2002). Two actin-binding proteins, gel-solin and alpha-actinin, which are regulated by both PIP2 and Ca2+ were found to be abnormally distributed. Actin polymerization plays a key role in cell -cell contacts, which may be defective in Lowe syndrome. 

Sbrissa, D., Ikonomov, O.C., Strakova, J., and Shisheva, A., 2004, Role for a novel signaling intermediate, phosphatidylinositol 5-phosphate, in insulin-regulated F-actin stress fiber breakdown and GLUT4 translocation. Endocrinology 145 4853 4865. 

Tillement, V., Lajoie-Mazenc, I., Casanova, A., Froment, C., Penary, M., Tovar, D., Marquez, R., Monsarrat, B., Favre, G., and Pradines, A. (2008). Phosphorylation of RhoB by CKl impedes actin stress fiber organization and epidermal growth factor receptor stabilization. Exp Cell Res 314 2811-2821. 

Nobes CD, Hall A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 1995 81 53-62. Nobes CD, Hall A. Rho, rac and cdc42 GTPases regulators of actin structures, cell adhesion and motility. Biochem. Soc. Trans. 1995 23 456-459. 

The three-dimensional network of actin stress fiber, which is an association of actin filaments, provides mechanical support for the cell, determines the cell shape, and enables cell movement. Thus the shape change in the cell due to the laser tsunami can be examined by observing the laser-induced dynamics of fibers. The actin stress fiber was visualized by binding it with enhanced green fluorescence protein (EGFP), and monitored by total internal reflection fluorescence (TIRF) imaging [34]. 

The actin cytoskeleton is important in cell shape changes, polarization, motility, chemotaxis, metastasis and ceU division, and Rho family proteins play critical roles in these effects. The involvement of PLD in changes in the actin cytoskeleton was first suggested by the effects of exogenous PLD and PA, which induced actin stress fiber formation and also increased the F-actin content of fibroblasts [172, 173]. Another study utilizing endotheUal ceUs also showed that PA that was free of LPA induced actin stress fiber formation [174]. Furthermore, the effects of LPA to induce this change in the actin cytoskeleton and also PA formation were blocked by butan-l-ol, but not butan-2-ol [174] (Fig. 4.6). 

Fig. 4.6 Inhibition of LPA-induced stress fiber formation in fibroblasts by prima7 butanol. Rat 1 fibroblasts were treated with LPA and actin stress fibers were visualized with...

Cell adhesion and motility E-Cadherin, a, -Catenin, FAK, Cadherin5, P-Se-lectin, ICAMs, LIMK1,2, pl30CAS, Integrins, PECAM, Paxillin, Talin, Calpain, FAK, Vincullin, Src, CSK, Actin stress fibers Peripheral vascular disease. Cancer... 

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