Cytoskeletal network

All eucaryotic cells contain various proteins in their cytoplasm that interact to form mechanically stabilizing structures. The amounts of these proteins differ with cell type, and the structural elements - collectively referred to as the cytoskeleton -can be very labile. Labile transformations of cytoskeletal networks are involved in such essential biological phenomena as chromosome movement and cell division, intracellular material transport, shape changes relating to tissue development, and amoeboid-like locomotion (1-3). A great deal of work in recent years has led to the biochemical characterization of numerous cytoskeletal proteins(A) and the elucidation of their spatial localization within a cell(2). However, few quantifiable models yet exist that are appropriate for incorporating that information into notions of shape transformation and cell movement(5-8). 

Black, M. M., Lasek, R. J. Slow components of axonal transport two cytoskeletal networks./. Cell Biol. 1980 86 616-623. 

The cytoskeletal network is responsible for the mechanical properties of the cell that modulate functions such as cell shape, locomotion, cytokinesis, and translocation of organelles. Experimental evidence suggests that the cytoskeleton also provides connections between cellular structures and presents a large surface area for interactions of various proteins and signaling molecules. Modulation of the cytoskeletal network may influence cell signaling, ion channels and intracellular calcium levels. Cytoskeleton is thus essential for regulation of cellular functions, cell integrity, and viability. 

This Chapter will highlight some of the features relating to the structure and construction of supramolecular structures that are primarily protein based. Examples of supramolecular structures found outside cells (extracellular matrices) and within cells (cytoskeletal networks) will be given that emphasize the relationships between the structure and function of these networks, the role of their frequently dynamic nature, and the genetic and congenital errors that can lead to, or be associated with, disease. 

A remarkable feature of cytoskeletal networks is that common elements can be incorporated into widely different structures in various parts of a cell. Networks can be dismantled in one part of a cell while other networks are being constructed from similar components in another. In fact, some networks undergo construction at one of their ends while simultaneously being dismantled at the other. 

In the fibroblast, and other cells, the concentration of monomeric actin can be as high as 200fiM and represent up to 50% of the total actin in the cell. This contrasts sharply with the critical concentration of ATP-actin in vitro which is typically 1 fxM or less. Thymosin (Mr = 5,000) is one protein that is responsible for sequestering monomeric actin in these cells. A large pool of monomeric actin provides the opportunity to rapidly assemble an actin-based cytoskeletal network while leaving preexisting actin-based networks intact. 

Principle In this procedure erythrocytes are treated with Triton X-100 which is reported to solubilize the membrane lipid leaving the underlying cytoskeletal network intact. The cyto-skeletons are separated from cytosolic components, Triton and solubilized lipid by centrifugation through a sucrose solution. The high salt concentration of the sucrose solution ensures the removal of residual lipid and integral membrane proteins from the cytoskeletal network. 

Fig. 2. Xenobiotic impact on glucocorticoid signaling. Xenobiotics impact on GR signaling could include either a direct effect on the GR signaling pathway and/or an indirect effect mediated by changes in other proteins/pathways. The direct effect encompasses impact on cortisol (F) binding to GR, their translocation, binding to GRE and initiation of transcription, whereas the indirect effect may include impact on kinases and phosphatases (K), accessory proteins (AP), the cytoskeletal network (C) and the proteasomal pathways (P), all of which are involved in GR signaling (see text for details).

It is not implausible to propose that at a relatively early time in evolution, cells were able to devise ways of escaping the chaos of solution chemistry. One method would be the attachment of their enzymes to a framework that is under the cell s control. Whereas prokaryotic cells are small enough to allow solution-based metabolism to occur, the dimensions of eukaryotic cells are unfavorable for many random processes. Based on what is now known about the intracellular environment, one may suggest that the MTL and cytoskeletal networks might be linked in the aqueous regions to key enzymes at their surfaces and that the regions between strands of the MTL are relatively dilute with respect to macromolecules. 

Figure 3.4 Fluid mosaic model of a biological membrane. This model represents a biological membrane as a sea of lipids with a mosaic of associated proteins either floating on the surface or embedded within a fluid bilayer of lipids. This model is sufficient to describe many phenomena associated with membranes. It has been modified more recently to include the concept of membrane domains constrained over different timescales by interactions among lipids, between lipids and proteins, and between membrane proteins and the cytoskeletal network. (Modified from a public-domain image created by Mariana Ruiz Villarreal.)...

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