Cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea.[2] In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components: microfilaments, intermediate filaments, and microtubules, and these are all capable of rapid growth or disassembly depending on the cell's requirements.[3]
A multitude of functions can be performed by the cytoskeleton. Its primary function is to give the cell its shape and mechanical resistance to deformation, and through association with extracellular connective tissue and other cells it stabilizes entire tissues.[4][5] The cytoskeleton can also contract, thereby deforming the cell and the cell's environment and allowing cells to migrate.[6] Moreover, it is involved in many cell signaling pathways and in the uptake of extracellular material (endocytosis),[7] the segregation of chromosomes during cellular division,[4] the cytokinesis stage of cell division,[8] as scaffolding to organize the contents of the cell in space[6] and in intracellular transport (for example, the movement of vesicles and organelles within the cell)[4] and can be a template for the construction of a cell wall.[4] Furthermore, it can form specialized structures, such as flagella, cilia, lamellipodia and podosomes. The structure, function and dynamic behavior of the cytoskeleton can be very different, depending on organism and cell type.[4][9][8] Even within one cell, the cytoskeleton can change through association with other proteins and the previous history of the network.[6]
A large-scale example of an action performed by the cytoskeleton is muscle contraction. This is carried out by groups of highly specialized cells working together. A main component in the cytoskeleton that helps show the true function of this muscle contraction is the microfilament. Microfilaments are composed of the most abundant cellular protein known as actin.[10] During contraction of a muscle, within each muscle cell, myosin molecular motors collectively exert forces on parallel actin filaments. Muscle contraction starts from nerve impulses which then causes increased amounts of calcium to be released from the sarcoplasmic reticulum. Increases in calcium in the cytosol allows muscle contraction to begin with the help of two proteins, tropomyosin and troponin.[10] Tropomyosin inhibits the interaction between actin and myosin, while troponin senses the increase in calcium and releases the inhibition.[11] This action contracts the muscle cell, and through the synchronous process in many muscle cells, the entire muscle.
History[edit]
In 1903, Nikolai K. Koltsov proposed that the shape of cells was determined by a network of tubules that he termed the cytoskeleton. The concept of a protein mosaic that dynamically coordinated cytoplasmic biochemistry was proposed by Rudolph Peters in 1929[12] while the term (cytosquelette, in French) was first introduced by French embryologist Paul Wintrebert in 1931.[13]
When the cytoskeleton was first introduced, it was thought to be an uninteresting gel-like substance that helped organelles stay in place.[14] Much research took place to try to understand the purpose of the cytoskeleton and its components.
Initially, it was thought that the cytoskeleton was exclusive to eukaryotes but in 1992 it was discovered to be present in prokaryotes as well. This discovery came after the realization that bacteria possess proteins that are homologous to tubulin and actin; the main components of the eukaryotic cytoskeleton.[15]
The cytoskeleton and cell mechanics[edit]
The cytoskeleton is a highly anisotropic and dynamic network, constantly remodeling itself in response to the changing cellular microenvironment. The network influences cell mechanics and dynamics by differentially polymerizing and depolymerizing its constituent filaments (primarily actin and myosin, but microtubules and intermediate filaments also play a role).[49] This generates forces, which play an important role in informing the cell of its microenvironment. Specifically, forces such as tension, stiffness, and shear forces have all been shown to influence cell fate, differentiation, migration, and motility.[49] Through a process called “mechanotransduction,” the cell remodels its cytoskeleton to sense and respond to these forces.
Mechanotransduction relies heavily on focal adhesions, which essentially connect the intracellular cytoskeleton with the extracellular matrix (ECM). Through focal adhesions, the cell is able to integrate extracellular forces into intracellular ones as the proteins present at focal adhesions undergo conformational changes to initiate signaling cascades. Proteins such as focal adhesion kinase (FAK) and Src have been shown to transduce force signals in response to cellular activities such as proliferation and differentiation, and are hypothesized to be key sensors in the mechanotransduction pathway.[50] As a result of mechanotransduction, the cytoskeleton changes its composition and/or orientation to accommodate the force stimulus and ensure the cell responds accordingly.
The cytoskeleton changes the mechanics of the cell in response to detected forces. For example, increasing tension within the plasma membrane makes it more likely that ion channels will open, which increases ion conductance and makes cellular change ion influx or efflux much more likely.[50] Moreover, the mechanical properties of cells determine how far and where, directionally, a force will propagate throughout the cell and how it will change cell dynamics.[51] A membrane protein that is not closely coupled to the cytoskeleton, for instance, will not produce a significant effect on the cortical actin network if it is subjected to a specifically directed force. However, membrane proteins that are more closely associated with the cytoskeleton will induce a more significant response.[50] In this way, the anisotropy of the cytoskeleton serves to more keenly direct cell responses to intra or extracellular signals.
Long-range order[edit]
The specific pathways and mechanisms by which the cytoskeleton senses and responds to forces are still under investigation. However, the long-range order generated by the cytoskeleton is known to contribute to mechanotransduction.[52] Cells, which are around 10–50 μm in diameter, are several thousand times larger than the molecules found within the cytoplasm that are essential to coordinate cellular activities. Because cells are so large in comparison to essential biomolecules, it is difficult, in the absence of an organizing network, for different parts of the cytoplasm to communicate.[53] Moreover, biomolecules must polymerize to lengths comparable to the length of the cell, but resulting polymers can be highly disorganized and unable to effectively transmit signals from one part of the cytoplasm to another. Thus, it is necessary to have the cytoskeleton to organize the polymers and ensure that they can effectively communicate across the entirety of the cell.
Common features and differences between prokaryotes and eukaryotes[edit]
By definition, the cytoskeleton is composed of proteins that can form longitudinal arrays (fibres) in all organisms. These filament forming proteins have been classified into 4 classes. Tubulin-like, actin-like, Walker A cytoskeletal ATPases (WACA-proteins), and intermediate filaments.[8][28]
Tubulin-like proteins are tubulin in eukaryotes and FtsZ, TubZ, RepX in prokaryotes. Actin-like proteins are actin in eukaryotes and MreB, FtsA in prokaryotes. An example of a WACA-proteins, which are mostly found in prokaryotes, is MinD. Examples for intermediate filaments, which have almost exclusively been found in animals (i.e. eukaryotes) are the lamins, keratins, vimentin, neurofilaments, and desmin.[8]
Although tubulin-like proteins share some amino acid sequence similarity, their equivalence in protein-fold and the similarity in the GTP binding site is more striking. The same holds true for the actin-like proteins and their structure and ATP binding domain.[8][28]
Cytoskeletal proteins are usually correlated with cell shape, DNA segregation and cell division in prokaryotes and eukaryotes. Which proteins fulfill which task is very different. For example, DNA segregation in all eukaryotes happens through use of tubulin, but in prokaryotes either WACA proteins, actin-like or tubulin-like proteins can be used. Cell division is mediated in eukaryotes by actin, but in prokaryotes usually by tubulin-like (often FtsZ-ring) proteins and sometimes (Thermoproteota) ESCRT-III, which in eukaryotes still has a role in the last step of division.[8]