The cytoskeleton is a three-dimensional structure in all eukaryotic cells and therefore can be found in neurons.
Although it does not differ much from other somatic cells, the cytoskeleton of neurons has its own characteristics, In addition to being important when they have defects, as is the case with Alzheimer’s disease.
Below we will see the three types of filaments that make up this structure, their peculiarities compared to other cytoskeletons and how it is affected in Alzheimer’s disease.
The neuron’s cytoskeleton
The cytoskeleton is one of the defining elements of eukaryotic cellsThat 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 scaffolding on which organelles are supported, organizing the cytosol and the vesicles within it, such as lysosomes.
Neurons are eukaryotic cells that specialize in making connections with others and forming the nervous system, and like any other eukaryotic cell, neurons have a cytoskeleton. The neuron’s cytoskeleton, structurally speaking, is not much different from that of any other cell, possessing microtubules, intermediate filaments, and actin filaments.
Below, we’ll look at each of these three types of filaments or tubes, explaining how the neuron’s cytoskeleton differs from that of other somatic cells.
The microtubules in the neuron are not much different from those found in other cells in the body. Its main structure consists of a polymer of 50 kDa tubulin subunits, Which is screwed so as to form an empty tube with a diameter of 25 nanometers.
There are two types of tubulin: alpha and beta. The two are not very different proteins, with close to 40% sequential similarity. It is these proteins which constitute the hollow tube, by the formation of protofilaments which join laterally, thus forming the microtubule.
Tubulin is an important substance because their dimers are responsible for the junction of two molecules of guanosine triphosphate (GTP), Dimers which have the capacity to exert an enzymatic activity on these same molecules. It is through this GTPase activity that the formation (assembly) and disassembly (disassembly) of the microtubules themselves take place, which gives them flexibility and the ability to modify the structure of the cytoskeleton.
Axon microtubules and dendrites are not continuous in the cell bodyThey are also not associated with a visible MTOC (microtubule organization center). Axonal microtubules can be 100 microns long, but have uniform polarity. In contrast, dendrite microtubules are shorter, exhibiting mixed polarity, with only 50% of their microtubules oriented towards the distal end in the cell body.
Although the microtubules of neurons are made up of the same components that are found in the rest of cells, it should be noted that they can have some differences. Microtubules in the brain contain tubulins of different isotypes and with a variety of proteins associated with them. Outraged, the composition of microtubules varies depending on the location in the neuron, Such as axons or dendrites. This suggests that brain microtubules could specialize in different tasks, depending on the unique environments granted by the neuron.
As with microtubules, intermediate filaments are components of both the neuronal cytostructure and that of any other cell. these filaments they play a very interesting role in determining the degree of specificity of the cell, 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, classified from I to V and, among them, those that can be found in the neuron:
Type I and II intermediate filaments are keratinous in nature and can be found in various combinations with epithelial cells in the body.. In contrast, type III ones 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 in mature astrocytes.
Type IV intermediate filaments are specific to neurons, exhibiting a common pattern between exons and introns, Which differ considerably from those of the three types above. Type V are those found in nuclear lamellae, forming the part that surrounds the nucleus of the cell.
Although these five different types of intermediate filaments are more or less specific to certain cells, it should be mentioned that the nervous system contains a variety of them. Despite their molecular heterogeneity, all of the intermediate filaments in eukaryotic cells occur, as we mentioned, as rope-like fibers, 8 to 12 nanometers in diameter.
Neural filaments it can be hundreds of micrometers in length, in addition to having protrusions in the form of side arms. In contrast, in other somatic cells, such as glial and non-neuronal cells, these filaments are shorter, with no side arms.
The main type of intermediate filament that can be found in the myelinated axons of the neuron is formed of three protein subunits, forming a triplet: a high molecular weight subunit (NFH, from 180 to 200 kDa), a medium molecular weight subunit (NFM, 130-170 kDa) and a low molecular weight subunit (NFL, 60-70 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 those of the nervous system are type IV, other filaments can also be found there. Vimentin is one of the proteins that make up type III filaments, Found in a wide variety of cells, including fibroblasts, microglia, and smooth muscle cells. They are also found in embryonic cells, as precursors of glia and neurons. Astrocytes and Schwann cells contain an acidic fibrillar glial protein, which forms type III filaments.
Actin microfilaments are the oldest components of the cytoskeleton. They consist of 43 kDa actin monomers, arranged as two chains of beads 4 to 6 nanometers in diameter.
Actin microfilaments can be found in neurons and glial cells, but are found particularly concentrated in presynaptic endings, dendritic spines, and neural growth cones.
What role does the neuronal cytoskeleton play in Alzheimer’s disease?
He had been discovered a relationship between the presence of beta-amyloid peptides, plaque components that accumulate in the brain in Alzheimer’s disease, And the rapid loss of neural cytoskeleton dynamics, especially in dendrites, where nerve impulses are received. Being less dynamic since, the transmission of information becomes less efficient, in addition to decreasing synaptic activity.
In a healthy neuron, their cytoskeleton is made up of actin filaments which, although anchored, have a certain flexibility. In order for the necessary dynamism to take place so that the neuron can adapt to the demands of the environment, there is a protein, cofilin 1, which is responsible for cutting actin filaments and separating their units. So, the structure changes shape, but if cofilin 1 is phosphorylated, that is, a phosphorus atom is added, it stops working.
Exposure to beta-amyloid peptides has been shown to induce an increase in cofilin 1 phosphorylation. This results in a loss of cytoskeletal dynamism, as the actin filaments stabilize and the structure loses flexibility. Dendritic spines lose their function.
One of the causes that makes cofilin 1 phosphorylate is when the enzyme ROCK (Rho-kinase) works on it.. This enzyme phosphorylates molecules, inducing or deactivating their activity, and would be one of the causes of the symptoms of Alzheimer’s disease, since it deactivates cofilin 1. To avoid this effect, especially during the early stages of disease, there is the drug Fasucil, which inhibits the action of this enzyme and prevents cofilin 1 from losing its function.
- Molina, I .. (2017). Cytoskeleton and neurotransmission. Molecular basis and protein interactions of vesicular transport and fusion in a neuroendocrine model. UMH doctoral journal. 2. 4. 10.21134 / doctumh.v2i1.1263.
- Kirkpatrick LL, Brady ST. Molecular components of the neuronal cytoskeleton. A: Siegel GJ, Agranoff BW, Albers RW, et al., Editors. Basic neurochemistry: molecular, cellular and medical aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999. Available at: https://www.ncbi.nlm.nih.gov/books/NBK28122/
- Rush, T. et al (2018) Synaptotoxicity in Alzheimer’s disease involved deregulation of actin cytoskeleton dynamics by cofilin 1 phosphorylation The Journal of Neuroscience doi: 10.1523 / JNEUROSCI.1409-18.2018