At the light-optical level, in a neuron and its processes, when stained with silver salts, a thin network of filaments, 0.5–3 microns thick, called “neurofibrils,” is revealed. It turned out that these are bundles of cytoskeletal fibrils different types, sticking together into bundles under the action of fixation.
Cytoskeleton nerve cell has great value in the life activity of neurons, and, as in other animal and human cells, consists of microtubules, intermediate filaments and microfilaments.
Microtubules.
Most microtubules are formed from the protein tubulin in the cytoplasm in the so-called. “microtubule organizing center, MTOC”, located in the area of the cell center (centriole). The microtubule wall consists of 13 concentrically located globules of the protein tubulin. Each tubulin molecule is a dimer and consists of α and ß-tubulin. The diameter of the microtubule is constant and amounts to 24 nm along the outer edge and 15 nm along the inner contour. The length of microtubules can be very different, from several tens of nanometers to tens of microns. This depends on the type of nerve cell, the location of microtubules in the neuron and processes. In neurons, microtubules are present in two forms - long, stable, and usually immobile microtubules and short, mobile microtubules. In neurons, with the help of special enzymes - katanin and spastin - the transformation of microtubules from one type to another occurs. Katanin cuts long stable microtubules into short mobile fragments (about 10 nm in length), which can then move through the cytoplasm and processes of the neuron for tens and hundreds of microns, after which short fragments of microtubules, possibly with the participation of spastin, can again assemble into long stable forms . (Fig. 1).
Each microtubule has a rapidly growing " + " - the end where the active assembly of new fragments takes place and " - " - the end where the growth of the microtubule is blocked by special “capping” proteins, which promotes the growth of the microtubule at the (+) end. In the neuron body the bulk of microtubules are oriented radially in the direction from the MTOC (minus end) to the cell periphery (plus end). Some microtubules in the cytoplasm of a neuron can be oriented in the opposite direction. In neuron processes, microtubules are located, as a rule, in an orderly manner and along the long axis of the processes. The average distance between adjacent individual microtubules ranges from 20 to 60 nm . (Fig. 2).
IN axon There are several types of microtubules. Most are located singly along the long axis of the axon and their plus end is directed towards the axon terminal (synapse). At the point where the axon departs from the cell body, at
so-called “axon hillock”, microtubules form compact bundles of 10-25 pieces, also oriented towards the periphery of the axon. (Fig. 2, a). This is where the sorting of material transported further along the axon occurs. In the axon, microtubules are more stable and less susceptible to various factors than in the neuron body and dendrites. IN synapse area a special type of microtubules was discovered - “curved microtubules” - they take part in the transport of synaptic vesicles with mediators directly to the presynaptic membrane.
IN dendrites microtubules (Fig. 2 b-d) are located along the axis of the process, but the orientation of their ends may be opposite to each other. This is typical, however, only for the proximal areas of dendrites (in the distal areas " + " - the end of the microtubules is directed towards the periphery).
An important element The structure of microtubules, which largely determines their properties, is the presence of a large number of specialized microtubule-associated proteins (MAP proteins). There are two main types of these proteins: 1) high molecular weight MAP proteins of several classes (MAP1-5); 2) low molecular weight tau proteins (some types of the latter are found only in neurons). The role of MAP proteins in the organization of the cytoskeleton of nervous tissue is very important: they ensure the stability of microtubules, controlling the processes of assembly and disassembly, connect microtubules with each other and with other components of the cytoskeleton, and also with plasma membrane and cell organelles. It is the differences in the structure of MAP proteins that determine the specificity of microtubules in the neuron body, axon and dendrites, since the structure of the microtubules themselves is the same everywhere. An example is the MAP-2a,b protein, which is present only in dendrites, while the MAP-3 protein is found only in axons and glia. If the synthesis of tau proteins is blocked in a culture of neuronal cells, then they lose their axons, retaining only dendrites. Introduction of tau protein genes into mutant nerve cells that do not express this protein leads to active growth of cell processes.
All processes associated with the formation of microtubules, their mobility and participation in cellular processes involve the expenditure of energy from GTP and GDP molecules. The stability of microtubules is associated with a number of both internal and external factors. Among the external ones, the following should be noted: the level of Ca +2 and Mg +2 ions in the neuron, temperature (the lower the temperature, the lower the rate of microtubule assembly and transport speed), the level of oxygen in the brain, pH of the environment (the higher the pH, the more intense there are processes of microtubule disintegration) and others. The average half-life of a microtubule in a neuron is ~10 - 20 minutes.
Blockade of polymerization or depolymerization of microtubules and, as a consequence, disruption of transport processes in neurons is caused by the influence of such substances - cytostatics, such as colchicine, colcemid, vinprestin, vinblastine, nocadazole, taxol. They are used in tumor chemotherapy to block the division of cancer cells.
Thus, in a neuron and its processes, microtubules are in a constant process of assembly, disassembly, and movement throughout the cytoplasm of the neuron. This state of the microtubule skeleton of the cell is called “dynamic instability of the cytoskeleton.”
Neurofilaments (intermediate filaments) .
In humans, more than 65 genes are associated with the synthesis of filamentous proteins. Connecting with each other, individual neurofilamentous proteins (monomers) first form homodimers of two fibrils in nerve cells, which then join in pairs and form a mature protofibril - a homotetramer, which consists of four identical protein molecules. Next, polymerization of neurofibrillary protofibrils occurs into a mature neurofibril, ~10 nm in diameter, and consisting of 8 long protofibrils. Neurofilaments are represented by three neurospecific proteins: NF-L, NF-H, NF-M. and are a kind of “ business card» neurons, because they are found only in nerve cells or cells of common origin with them.
The assembly of neurofilaments occurs quite quickly. In vitro experiments have shown that neurofilaments with a length of 60 nm are formed within the first seconds, 300 nm in the first minute, and after 15-20 minutes the length increases to 0.5 - 1 micron. The elongation process does not end there, and after several hours of assembly we have very long neurofilaments. Neurofilaments are oriented predominantly along the long axis of neuron processes. They can be either single or form bundles. There are especially many of them in the area of the axon hillock. In neurons of the central nervous system in Alzheimer's disease, multiple sclerosis and other pathologies, there is a sharp increase in the concentration of neurofilaments and a violation of their orientation with a clear decrease in the concentration of microtubules (Fig.3).
Neurofilaments are structures that are more stable than microtubules (the average half-life of neurofilaments is ~ 40 minutes). However, they are also in a state of “dynamic instability”, constantly being disassembled and reassembled in the body and processes of the neuron, with the help of special enzymes. There are no neurofilaments in the area of the synaptic terminal - in the presynaptic region they are destroyed and their components return to the axon and body of the neuron using reverse transport.
In general, intermediate filaments perform a mechanical function in a neuron, maintaining the shape of the body and processes. They are involved in the growth and regeneration of processes, and are also an important component of intracellular transport. Neurofilaments are closely associated with each other, with microtubules, cellular and axonal membranes and other cellular components, forming a complex three-dimensional cytoskeletal network in the body and processes of neurons.
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axon transport online, axon transport Minsk
Axon transport is the movement of various biological materials along the axon of a nerve cell.
The axonal processes of neurons are responsible for transmitting the action potential from the neuron body to the synapse. The axon is also a path along which the necessary biological materials are transported between the neuron body and the synapse, which is necessary for the functioning of the nerve cell. Membrane organelles (mitochondria), various vesicles, signaling molecules, growth factors, protein complexes, cytoskeletal components, and even Na+ and K+ channels are transported along the axon from the synthesis region in the neuron body. The final destinations of this transport are certain areas of the axon and synaptic plaque. in turn, neurotrophic signals are transported from the synapse area to the cell body. This acts as feedback, reporting the state of innervation of the target.
Peripheral axon length nervous system in humans can exceed 1 m, and may be more in large animals. The thickness of a large human motor neuron is 15 microns, which with a length of 1 m gives a volume of ~0.2 mm³, which is almost 10,000 times the volume of a liver cell. This makes neurons dependent on efficient and coordinated physical transport of substances and organelles along axons.
The lengths and diameters of axons, as well as the amount of material transported along them, certainly indicate the possibility of failures and errors in the transport system. Many neurodegenerative diseases are directly related to disruptions in the functioning of this system.
- 1 Main features of the axon transport system
- 2 Classification axon transport
- 3 See also
- 4 Literature
Main features of the axon transport system
Simply put, axon transport can be represented as a system consisting of several elements. it includes cargo, motor proteins that carry out transport, cytoskeletal filaments, or “rails” along which “motors” are able to move. Linker proteins are also required to link motor proteins with their cargo or other cellular structures, and auxiliary molecules that trigger and regulate transport.
Classification of axon transport
Cytoskeletal proteins are delivered from the cell body, moving along the axon at a speed of 1 to 5 mm per day. This is slow axonal transport (transport similar to it is also found in dendrites). Many enzymes and other cytosolic proteins are also transported using this type of transport.
Non-cytosolic materials that are needed at the synapse, such as secreted proteins and membrane-bound molecules, move along the axon at much higher speeds. These substances are transported from their site of synthesis, the endoplasmic reticulum, to the Golgi apparatus, which is often located at the base of the axon. These molecules, packaged in membrane vesicles, are then transported along microtubule rails by rapid axonal transport at a speed of up to 400 mm per day. Thus, mitochondria, various proteins, including neuropeptides (neurotransmitters of a peptide nature), and non-peptide neurotransmitters are transported along the axon.
The transport of materials from the neuron body to the synapse is called anterograde, and in the opposite direction - retrograde.
Transport along the axon over long distances occurs with the participation of microtubules. Microtubules in the axon have an inherent polarity and are oriented with the fast-growing (plus-) end towards the synapse, and the slow-growing (minus-) end towards the neuron body. Axon transport motor proteins belong to the kinesin and dynein superfamilies.
Kinesins are primarily plus-terminal motor proteins that transport cargo such as synaptic vesicle precursors and membrane organelles. This transport goes towards the synapse (anterograde). Cytoplasmic dyneins are minus-terminal motor proteins that transport neurotrophic signals, endosomes, and other cargo retrograde to the neuronal body. Retrograde transport is not exclusively carried out by dyneins: several kinesins have been found that move in a retrograde direction.
See also
- Wallerian degeneration
- Kinesin
- Dineen
- DISC1
Literature
- Duncan J.E., Goldstein L.S. The genetics of axonal transport and axonal transport disorders. // PLoS Genet. 2006 Sep 29;2(9):e124. PLoS Genetic, PMID 17009871.
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axon transport Minsk, axon transport online, axon transport Ternopil, axon transport
Axon Transport Information About
Of particular interest, from the point of view of the physiology of the central nervous system, is the process of intracellular transport, transmission of information and signals in the axon of a nerve cell. The diameter of the axon of a nerve cell is only a few microns. At the same time, the length of the axon reaches 1 m in some cases. How is a constant and high speed of transport along the axon ensured?
For this purpose, a special axon transport mechanism is used, which is divided into fast and slow.
Firstly, it should be kept in mind that a fast transport mechanism is anterograde, i.e. directed from the cell body to the axon.
Secondly, the main “vehicle” for fast axonal transport are vesicles (vesicles) and some structural formations of the cell (for example, mitochondria), which contain substances intended for transport. Such particles make short, rapid movements, which corresponds to approximately 5 µm s(-1). Fast axonal transport requires a significant concentration of ATP energy.
Third, slow axonal transport moves individual cytoskeletal elements: tubulin and actin. For example, tubulin, as an element of the cytoskeleton, moves along the axon at a speed of about 1 mm day(-1). The speed of slow axonal transport is approximately equal to the speed of axon growth.
The processes of regulation of effects on the cell membrane are important for understanding the physiology of the central nervous system. The main mechanism of such regulation is a change in membrane potential. Changes in membrane potential are caused by the influence of neighboring cells or changes in the extracellular ion concentration.
The most significant regulator of membrane potential is the extracellular substance in interaction with specific receptors on the plasma membrane. These extracellular substances include synaptic mediators that transmit information between nerve cells.
Synaptic transmitters are small molecules released from nerve endings at the synapse. When they reach the plasma membrane of another cell, they trigger electrical signals or other regulatory mechanisms (Fig. 6).
Rice. 6. Scheme of release of mediators and processes occurring in the synapse
In addition, individual chemical agents (histamine, prostaglandin) move freely in the extracellular space, which are quickly destroyed, but have a local effect: they cause short-term contraction of smooth muscle cells, increase the permeability of the vascular endothelium, cause a sensation of itching, etc. Certain chemical agents promote nerve growth factors. In particular, for the growth and survival of sympathetic neurons.
In fact, there are two information transmission systems in the body: nervous and hormonal (for details, see unit 2).
Group A fibers alpha
(diameter -13-22 microns, speed - 60-120 m/s, AP duration - 0.4-0.5 ms)
1). efferent fibers that conduct
excitation to skeletal muscles from alpha motor neurons
2) afferent fibers that conduct excitation from muscle receptors to the central nervous system
Group A beta fibers
(diameter – 8-13-µm, speed – 40-70 m/s, AP duration – 0.4-0.6 ms)
1. Afferent fibers conducting
excitation from touch receptors and tendon receptors in the central nervous system
Group A gamma fibers
(diameter – 4-8 microns, speed – 15-40 m/s, AP duration – 0.5-0.7 ms)
1) efferent fibers to muscle spindles from gamma motor neurons
2). afferent fibers that conduct
excitation from touch and pressure receptors in the central nervous system
Group B fibers
(diameter - 1-3 microns, speed -3-14 m/s, AP duration - 1.2 ms)
These are preganglionic fibers of the autonomic nervous system
Group C fibers
(diameter - 0.5-1.0 µm, speed -0.5-2.0 m/s, AP duration - 2.0 ms)
1. postganglionic fibers of the ANS
2. afferent fibers that conduct excitation from pain, pressure and heat receptors to the central nervous system
Axon transport. Fast axon transport. Slow axon transport.
Axon transport is the movement of substances along an axon. Proteins synthesized in the cell body, synaptic mediator substances and low molecular weight compounds move along the axon along with cellular organelles, in particular mitochondria. For most substances and organelles, transport in the opposite direction has also been detected. Viruses and toxins can enter the axon at its periphery and travel along it. Axon transport is an active process. Distinguish
fast axonal transport and slow axonal transport.
Slow axonal transport is the transport of large molecules; in this case, apparently, the transport mechanism itself is not slower, but the transported substances from time to time enter cellular compartments that are not involved in transport. Thus, mitochondria sometimes move at the speed of fast transport, then stop or change the direction of movement, resulting in slow transport.
The rate of fast axonal transport is 410 mm/day. This rate is found in all neurons of warm-blooded animals, regardless of the type of molecules transferred.
In many cases, the transport of organelles in a cell depends on microtubules. Microtubules in the axon are characterized by relative stability compared to other cells. This is likely due to the high content of MAP, which are capable of stabilizing microtubules. In addition, this is facilitated by the formation of microtubule bundles with the help of various associated proteins.
There are two main types of transport: direct (anterograde) - from the cell body along the processes to their periphery and reverse (retrograde) - along the neuron processes to the cell body
In a neuron, as in other cells of the body, processes of disintegration of molecules, organelles, and other cell components constantly occur. They need to be constantly updated. Neuroplasmic transport is important for ensuring the electrical and non-electrical functions of the neuron, for providing feedback between the processes and the body of the neuron. When nerves are damaged, regeneration of damaged areas and restoration of innervation of organs is necessary.
A variety of substances are transported along the processes of the neuron with at different speeds, in different directions and using different transport mechanisms. There are two main types of transport: direct (anterograde) - from the cell body along the processes to their periphery and reverse (retrograde) - along the neuron processes to the cell body (Table 1).
Five groups of “motor” proteins, closely associated with the cytoskeletal network, participate in the implementation of transport processes in a neuron. They include proteins such as kinesins, deneins and myosins.
Five groups of the so-called are involved in the implementation of transport processes in a neuron. “motor” molecules (Fig. xx).
Mechanisms of axonal and dendritic transport
Direct axonal transport is carried out by motor molecules associated with the cytoskeletal system and the plasma membrane. The motor part of kinesin or denein molecules binds to the microtubule, and its tail part binds to the transported material, to the axonal membrane, or to neighboring cytoskeletal elements. A number of auxiliary proteins (adaptors) associated with kinesin or denein also take part in ensuring transport along the processes. All processes require significant energy consumption.
Reverse (retrograde) transport.
In axons, the main mechanism of reverse transport is the system of denein and myosin motor proteins. The morphological substrate of this transport is: in the axon - multivesicular bodies and signaling endosomes, in dendrites - multivesicular and multilamellar bodies.
In dendrites, reverse transport is carried out by molecular complexes of not only denein, but also kinesin. This is due to the fact that (as mentioned earlier) in the proximal areas of dendrites, microtubules are oriented in mutually opposite directions, and the transport of molecules and organelles to the “+” end of microtubules is carried out only by kinesin complexes. As with direct transport, different components and substances are transported retrogradely in different neurons at different rates, and presumably in different ways.
The smooth endoplasmic reticulum plays a major role in transport processes in the neuron. It has been shown that a continuous branched network of smooth reticulum cisterns extends along the entire length of the neuron processes. The terminal branches of this network penetrate into the presynaptic areas of synapses, where synaptic vesicles are detached from them. It is through its tanks that many mediators and neuromodulators, neurosecrets, enzymes of their synthesis and breakdown, calcium ions and other components of the axotok are quickly transported. The molecular mechanisms of this type of transport are not yet clear.
5.2.5. AXON TRANSPORT
The presence of processes in a neuron, the length of which can reach 1 m (for example, axons innervating the muscles of the limbs), creates a serious problem of intracellular communication between different parts of the neuron and the elimination of possible damage to its processes. The bulk of substances (structural proteins, enzymes, polysaccharides, lipids, etc.) are formed in the trophic center (body) of the neuron, located mainly near the nucleus, and they are used in various parts of the neuron, including its processes. Although axon terminals provide synthesis of transmitters, ATP, and recycling of the vesicle membrane after release of the transmitter, a constant supply of enzymes and membrane fragments from the cell body is still required. Transport of these substances (eg proteins) by diffusion over a distance equal to the maximum length of the axon (about 1 m) would take 50 years! To solve this problem, evolution has formed special type transport within neuron processes, which is more well studied in axons and is called axonal transport. With the help of this process, a trophic influence is carried out not only within different parts of the neuron, but also on the innervated
washable cells. Recently, data have appeared on the existence of neuroplasmic transport in dendrites, which is carried out from the cell body at a speed of about 3 mm per day. There are fast and slow axon transport.
A. Fast axon transport goes in two directions: from the cell body to the axon endings (antegrade transport, speed 250-400 mm/day) and in the opposite direction (retrograde transport, speed 200-300 mm/day). Through antegrade transport, vesicles formed in the Golgi apparatus and containing membrane glycoproteins, enzymes, mediators, lipids and other substances are delivered to axon endings. Through retrograde transport, vesicles containing remnants of destroyed structures, membrane fragments, acetylcholinesterase, and unidentified “signal substances” that regulate protein synthesis in the cell soma are transferred to the neuron body. Under pathological conditions, polio, herpes, rabies viruses and tetanus exotoxin can be transported along the axon to the cell body. Many substances delivered by retrograde transport are destroyed in lysosomes.
Fast axonal transport is carried out with the help of special structural elements of the neuron: microtubules and microfilaments, some of which are actin filaments (actin makes up 10-15% of neuron proteins). Transport requires ATP energy. Destruction of microtubules (for example, by colchicine) and microfilaments (by cytocholasin B), a decrease in the level of ATP in the axon by more than 2 times, and a drop in Ca 2+ concentration block axonal transport.
B. Slow axon transport occurs only in the antegrade direction and represents the movement of the entire column of axoplasm. It is detected in experiments with compression (ligation) of the axon. In this case, there is an increase in the diameter of the axon proximal to the constriction as a result of the “influx of hyaloplasm” and a thinning of the axon behind the place of compression. The speed of slow transport is 1-2 mm/day, which corresponds to the speed of axon growth in ontogenesis and during its regeneration after damage. With the help of this transport, microtubule and microfilament proteins formed in the endoplasmic reticulum (tubulin, actin, etc.), cytosolic enzymes, RNA, channel proteins, pumps and other substances move. Slow axon transport is not
collapses when microtubules are destroyed, but stops when the axon separates from the neuron body, which indicates different mechanisms of fast and slow axon transport.
B. Functional role of axon transport. 1. Antegrade and retrograde transport of proteins and other substances are necessary to maintain the structure and function of the axon and its presynaptic terminals, as well as for processes such as axonal growth and the formation of synaptic contacts.
2. Axon transport is involved in the trophic influence of the neuron on the innervated cell, since some of the transported substances are released into the synaptic cleft and act on receptors of the postsynaptic membrane and nearby areas of the membrane of the innervated cell. These substances participate in the regulation of metabolism, processes of reproduction and differentiation of innervated cells, forming their functional specificity. For example, in experiments with cross innervation of fast and slow muscles, it was shown that muscle properties change depending on the type of innervating neuron and its neurotrophic effect. The transmitters of the trophic influences of the neuron have not yet been precisely determined; polypeptides and nucleic acids are of great importance in this regard.
3. The role of axon transport is especially clearly revealed in cases of nerve damage. If a nerve fiber is interrupted in any area, its peripheral segment, deprived of contact with the body of the neuron, undergoes destruction, which is called Wallerian degeneration. Within 2-3 days, the breakdown of neurofibrils, mitochondria, myelin and synaptic endings occurs. It should be noted that a section of the fiber undergoes decay, the supply of oxygen and nutrients through the bloodstream does not stop. It is believed that the decisive mechanism of degeneration is the cessation of axonal transport of substances from the cell body to synaptic endings.
4. Axon transport also plays an important role in the regeneration of nerve fibers.
