Neuron cytoskeleton: parts and functions

The cytoskeleton is a three-dimensional structure in all eukaryotic cells and can therefore be found in neurons.

Although it does not differ much from other somatic cells, the cytoskeleton of neurons has some characteristics of its ownIn addition to being important when they have defects, as is the case with Alzheimer's disease.

Next we will see the three types of filaments that make up this structure, their peculiarities with respect to the rest of the cytoskeletons and how it is affected in Alzheimer's.

• Related article: "What are the parts of the neuron?"

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 which 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 found in it, such as lysosomes.

Neurons are eukaryotic cells specialized in forming connections with others and constituting the nervous system and, as with any other eukaryotic cell, neurons possess 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 see 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 microtubules of the neuron are not very different from those that can be found in other cells of 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 sequence similarity close to 40%. It is these proteins that constitute the hollow tube, through the formation of protofilaments that come together laterally, thus forming the microtubule.

Tubulin is an important substance, since its dimers 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 it is involved in the formation (assembly) and disassembly (disassembly) of the microtubules themselves, giving flexibility and ability to modify the cytoskeletal structure.

Axon microtubules and dendrites are not continuous with the cell body, nor are they associated with any visible MTOC (microtubule organizing center). Axonal microtubules can be 100 μm in length, but have 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 other cells, it should be noted that they may present some differences. The microtubules of the brain contain tubulins of different isotypes, and with a variety of proteins associated with them. What's more, microtubule composition varies based on location within the neuron, Like the axons waves dendrites. This suggests that microtubules in the brain could specialize in different tasks, depending on the unique environments that the neuron provides.

Intermediate filaments

As with microtubules, intermediate filaments are components as much of the neuronal cytostructure as that of any other cell. These filaments 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 resemble a rope.

In the body 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 keratin in nature and can be found in various combinations with epithelial cells of the body.. In contrast, type III cells can be found in less differentiated cells, such as glial cells or precursors. neuronal cells, although they have also been seen in more formed cells, such as those that make up smooth muscle tissue and in astrocytes mature.

Type IV intermediate filaments are specific to neurons, presenting a common pattern between exons and introns., which differ significantly from those of the three previous 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 diversity of these. Despite their molecular heterogeneity, all intermediate filaments in eukaryotic cells are They present, as we have mentioned, as fibers that resemble a rope, with a diameter between 8 and 12 nanometers.

The neural filaments can be hundreds of micrometers long, in addition to having projections in the form of lateral arms. In contrast, in other somatic cells, such as those of the glia and non-neuronal cells, 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 made up of three protein subunits, forming a triplet: a high molecular weight subunit (NFH, 180 to 200 kDa), a medium molecular weight subunit (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 typical 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 precursors to glia 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 up of 43-kDa actin monomers, which are organized as if they were two strings of beads, with diameters of 4 to 6 nanometers.

Actin microfilaments can be found in neurons and glial cells, but they are found especially concentrated in presynaptic terminals, dendritic spines and growth cones neural.

What role does the neuronal cytoskeleton play in Alzheimer's?

It has been found a relationship 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 the dendrites, where the nerve impulse is received. As this part is less dynamic, the transmission of information becomes less efficient, in addition to decreasing synaptic activity.

In a healthy neuron, its cytoskeleton is made up of actin filaments that, although anchored, have some flexibility. So that the necessary dynamism is given 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. Thus, the structure changes shape, however, if cofilin 1 is phosphorylated, that is, a phosphorous atom is added, 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, since the actin filaments stabilize, and the structure loses flexibility. Dendritic spines lose function.

One of the causes that make cofilin 1 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.

Bibliographic references:

• Molina, Y.. (2017). Cytoskeleton and neurotransmission. Molecular bases and protein interactions of vesicular transport and fusion in a neuroendocrine model. UMH Doctorate Magazine. 2. 4. 10.21134 / doctumh.v2i1.1263.
• Kirkpatrick LL, Brady ST. Molecular Components of the Neuronal Cytoskeleton. In: Siegel GJ, Agranoff BW, Albers RW, et al., Editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999. Available from: https://www.ncbi.nlm.nih.gov/books/NBK28122/
• Rush, T. et al (2018) Synaptotoxicity in Alzheimer's disease involved a dysregulation of actin cytoskeleton dynamics through cofilin 1 phosphorylation The Journal of Neuroscience doi: 10.1523 / JNEUROSCI.1409-18.2018