The cytoskeleton (also CSK) is a cellular "scaffolding" or "skeleton" contained within a cell’s cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton. It has structures such as flagella, cilia and lamellipodia and plays important roles in both intracellular transport (the movement of vesicles and organelles, for example) and cellular division. In 1903 Nikolai K Koltsov proposed that the shape of cells was determined by a network of tubules which he termed the cytoskeleton. The concept of a protein mosaic that dynamically coordinated cytoplasmic biochemistry was proposed by Rudolph Peters in 1929 while the term (cytosquelette, in French) was first introduced by French embryologist Paul Wintrebert in 1931.
The eukaryotic cytoskeleton
Actin cytoskeleton of mouse embryo fibroblasts, stained with phalloidin. (Right side)
Eukaryotic cells contain three main kinds of cytoskeletal filaments, which are microfilaments, intermediate filaments, and microtubules. The cytoskeleton provides the cell with structure and shape, and by excluding macromolecules from some of the cytosol it adds to the level of macromolecular crowding in this compartment. Cytoskeletal elements interact extensively and intimately with cellular membranes. A number of small molecule cytoskeletal drugs have been discovered that interact with actin and microtubules. These compounds have proven useful in studying the cytoskeleton and several have clinical applications.
Microfilaments (actin filaments)
These are the thickest filaments of the cytoskeleton. They are composed of linear polymers of actin subunits, and generate force by elongation at one end of the filament coupled with shrinkage at the other, causing net movement of the intervening strand. They also act as tracks for the movement of myosin molecules that attach to the microfilament and "walk" along them. Actin structures are controlled by the Rho family of small GTP-binding proteins such as Rho itself for contractile acto-myosin filaments ("stress fibers"), Rac for lamellipodia and Cdc42 for filopodia.
These filaments, averaging 10 nanometers in diameter, are more stable (strongly bound) than actin filaments, and heterogeneous constituents of the cytoskeleton. Like actin filaments, they function in the maintenance of cell-shape by bearing tension (microtubules, by contrast, resist compression. It may be useful to think of micro- and intermediate filaments as cables, and of microtubules as cellular support beams). Intermediate filaments organize the internal tridimensional structure of the cell, anchoring organelles and serving as structural components of the nuclear lamina and sarcomeres. They also participate in some cell-cell and cell-matrix junctions.
Different intermediate filaments are:
made of vimentins, being the common structural support of many cells.
made of keratin, found in skin cells, hair and nails.
Neurofilaments of neural cells.
Made of lamin, giving structural support to the nuclear envelope.
Microtubules are hollow cylinders about 23 nm in diameter (lumen = approximately 15 nm in diameter), most commonly comprising 13 protofilaments which, in turn, are polymers of alpha and beta tubulin. They have a very dynamic behaviour, binding GTP for polymerization. They are commonly organized by the centrosome.
In nine triplet sets (star-shaped), they form the centrioles, and in nine doublets oriented about two additional microtubules (wheel-shaped) they form cilia and flagella. The latter formation is commonly referred to as a "9+2" arrangement, where in each doublet is connected to another by the protein dynein. As both flagella and cilia are structural components of the cell, and are maintained by microtubules, they can be considered part of the cytoskeleton.
They play key roles in:
Intracellular transport (associated with dyneins and kinesins, they transport organelles like mitochondria or vesicles).
the axoneme of cilia and flagella.
the mitotic spindle.
synthesis of the cell wall in plants.
The prokaryotic cytoskeleton
The cytoskeleton was previously thought to be a feature only of eukaryotic cells, but homologues to all the major proteins of the eukaryotic cytoskeleton have recently been found in prokaryotes. Although the evolutionary relationships are so distant that they are not obvious from protein sequence comparisons alone, the similarity of their three-dimensional structures and similar functions in maintaining cell shape and polarity provides strong evidence that the eukaryotic and prokaryotic cytoskeletons are truly homologous. However, some structures in the bacterial cytoskeleton may have yet to be identified.
FtsZ was the first protein of the prokaryotic cytoskeleton to be identified. Like tubulin, FtsZ forms filaments in the presence of GTP, but these filaments do not group into tubules. During cell division, FtsZ is the first protein to move to the division site, and is essential for recruiting other proteins that synthesize the new cell wall between the dividing cells.
MreB and ParM
Prokaryotic actin-like proteins, such as MreB, are involved in the maintenance of cell shape. All non-spherical bacteria have genes encoding actin-like proteins, and these proteins form a helical network beneath the cell membrane that guides the proteins involved in cell wall biosynthesis.
Some plasmids encode a partitioning system that involves an actin-like protein ParM. Filaments of ParM exhibit dynamic instability, and may partition plasmid DNA into the dividing daughter cells by a mechanism analogous to that used by microtubules during eukaryotic mitosis.
The bacterium Caulobacter crescentus contains a 3rd protein, crescentin, that is related to the intermediate filaments of eukaryotic cells. Crescentin is also involved in maintaining cell shape, such as helical and vibrioid forms of bacteria, but the mechanism by which it does this is currently unclear.