The cytoskeleton is a three-dimensional structure in all eukaryotic cells, and therefore can be found in neurons.
Although it is not very different from the rest of somatic cells, the cytoskeleton of neurons has some characteristics of its own, in addition to being important when they have defects, such as Alzheimer's disease.
Next we will see the three types of filaments that make up this structure, their particularities with respect to the rest of the cytoskeletons and how it is affected in Alzheimer's.
The cytoskeleton of the neuron
The cytoskeleton is one of the defining elements of eukaryotic cells, that is, those that have a defined nucleus, a structure that can be observed in animal and plant cells. This structure is, in essence, the internal scaffold on which the organelles are supported, organizing the cytosol and the vesicles that are in it, such as lysosomes.
Neurons are eukaryotic cells specialized in forming connections with others and constituting the nervous system, and, like any other eukaryotic cell, neurons possess a cytoskeleton. The cytoskeleton of the neuron, structurally speaking, is not very different from that of any other cell, possessing microtubules, intermediate filaments and actin filaments.
Below we will look at each of these three types of filaments or tubes, specifying how the cytoskeleton of the neuron differs from that of other somatic cells.
Microtubules
The neuron's microtubules are not very different from those found in other cells in the body. Its main structure consists of a 50-kDa tubulin subunit polymer, which is screwed in such a way that it forms a hollow tube with a diameter of 25 nanometers.
There are two types of tubulin: alpha and beta. Both are proteins not very different from each other, with a sequential similarity close to 40%. It is these proteins that constitute the hollow tube, through the formation of protofilaments that join laterally, thus forming the microtubule.
Tubulin is an important substance, since its dimers are what are responsible for joining two molecules of guanosine triphosphate (GTP), dimers which have the ability to perform enzymatic activity on these same molecules. It is through this GTPase activity that is involved in the formation (assembly) and disassembly (disassembly) of the microtubules themselves, giving flexibility and ability to modify the cytoskeletal structure.
The axon microtubules and dendrites are not continuous to the cell body, nor are they associated with any visible MTOC (Microtubule Organizing Center). Axonal microtubules can be 100 μm in length, but have a uniform polarity. In contrast, the microtubules of the dendrites are shorter, presenting mixed polarity, with only 50% of their microtubules oriented towards the termination distal to the cell body.
Although the microtubules of neurons are made up of the same components that can be found in the rest of the cells, it should be noted that they may have some differences. The microtubules of the brain contain tubulins of different isotypes, and with a variety of proteins associated with them. Furthermore, the composition of microtubules varies depending on the location within the neuron, such as axons or dendrites. This suggests that the microtubules of the brain could specialize in different tasks, depending on the unique environments provided by the neuron.
Intermediate filaments
As with microtubules, the intermediate filaments are components of both the neuronal cytostructure and that of any other cell. These filaments play a very interesting role in determining the degree of cell specificity, in addition to being used as markers of cell differentiation. In appearance, these filaments are reminiscent of a rope.
In the organism there are up to five types of intermediate filaments, ordered from I to V and, some of them being those that can be found in the neuron:
Type I and II intermediate filaments are keratinic in nature and can be found in various combinations with body epithelial cells. In contrast, type III can be found in less differentiated cells, such as glial cells or neuronal precursors, although they have also been seen in more formed cells, such as those that make up smooth muscle tissue and astrocytes. ripe.
Type IV intermediate filaments are specific to neurons, presenting a common pattern between exons and introns, which differ significantly from those of the previous three types. Type V are those found in the nuclear laminae, forming the part that surrounds the cell nucleus.
Although these five different types of intermediate filaments are more or less specific to certain cells, it is worth mentioning that the nervous system contains a diversity of these. Despite their molecular heterogeneity, all the intermediate filaments in eukaryotic cells appear, as we mentioned, as string-like fibers, with a diameter between 8 and 12 nanometers.
Neural filaments can be hundreds of micrometers long, in addition to having lateral arm-shaped projections. In contrast, in other somatic cells, such as glial and non-neuronal, these filaments are shorter, lacking lateral arms.
The main type of intermediate filament that can be found in the myelinated axons of the neuron is formed by three protein subunits, forming a triplet: a high molecular weight subunit (NFH, from 180 to 200 kDa), a molecular weight subunit medium (NFM, 130 to 170 kDa) and a low molecular weight subunit (NFL, 60 to 70 kDa). Each protein subunit is encoded by a separate gene. These proteins are those that make up type IV filaments, which are expressed only in neurons and have a characteristic structure.
But although the ones of the nervous system are type IV, other filaments can also be found in it. Vimentin is one of the proteins that make up type III filaments, present in a wide variety of cells, including fibroblasts, microglia, and smooth muscle cells. They are also found in embryonic cells, as glial precursors and neurons. Astrocytes and Schwann cells contain acidic fibrillar glial protein, which constitutes type III filaments.
Actin microfilaments
Actin microfilaments are the oldest components of the cytoskeleton. They are made of 43-kDa actin monomers, which are organized as if they were two strings of pearls, with diameters of 4 to 6 nanometers.
Actin microfilaments can be found in neurons and glial cells, but are especially concentrated in presynaptic terminals, dendritic spines, and neural growth cones.
What role does the neuronal cytoskeleton play in Alzheimer's?
A relationship has been discovered between the presence of beta-amyloid peptides, components of plaques that accumulate in the brain in Alzheimer's disease, and the rapid loss of dynamics of the neuronal cytoskeleton, especially in dendrites, where the impulse is received. nervous. As this part is less dynamic, the transmission of information becomes less efficient, in addition to reducing synaptic activity.
In a healthy neuron, its cytoskeleton is made up of actin filaments that, although anchored, have some flexibility. In order to give the necessary dynamism so that the neuron can adapt to the demands of the environment, there is a protein, cofilin 1, which is responsible for cutting the actin filaments and separating their units. Thus, the structure changes shape, however, if cofilin 1 is phosphorylated, that is, a phosphorus atom is added to it, it stops working correctly.
Exposure to beta-amyloid peptides has been shown to induce increased phosphorylation of cofilin 1. This causes the cytoskeleton to lose dynamism as the actin filaments stabilize and the structure loses flexibility. Dendritic spines lose function.
One of the causes that cause cofilin 1 to phosphorylate is when the enzyme ROCK (Rho-kinase) acts on it. This enzyme phosphorylates molecules, inducing or deactivating their activity, and would be one of the causes of Alzheimer's symptoms, since it deactivates cofilin 1. To avoid this effect, especially during the early stages of the disease, there is the drug Fasucil, which inhibits the action of this enzyme and prevents cofilin 1 from losing its function.
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