There are two main types of transport: direct (anterograde) - from the cell body along the processes to their periphery and reverse (retrograde) - along the processes of the neuron to the cell body - Studopedia. Cytoskeleton of a neuron

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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.

The length of the axon of the human peripheral nervous system can exceed 1 m, and may be longer 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 of 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. Also required are linker proteins that connect motor proteins to 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 speeds 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

  1. 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 Information About


In a neuron, as in other cells of the body, processes of decay of molecules, organelles, and other cell components are constantly occurring. 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.

Various substances are transported along neuron processes 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).

Table 1 The main components of axonal and dendritic transport in vertebrate neurons (according to various authors)

Transport components and subcomponents

Speed

mm/day

What is transported

Morphological substrate of transport

Direct (anterograde) axonal transport
Fast
I 200- 500 Mediators and their precursors, enzymes for the synthesis of mediators, plasma membrane proteins, membrane organelles, neurohormones, Synaptic vesicles, smooth reticulum cisterns, neurosecretory granules, cytoskeletal network
Intermediate
II 50 - 100 Mitochondrial proteins, membrane lipids Mitochondria, cytoskeleton
III 15 Myosin proteins Cytoskeleton
Slow
IV SCb 2- 4 Actin, clathrin, actin-binding proteins, neuronal metabolic enzymes, axoplasmic proteins
VSCa 0,2- 1 Neurofilament proteins, tubulin and microtubule fragments, axoplasmic enzymes Cytoskeleton (microtubules, micro- and neurofilaments), microtrabecular meshwork

Direct fast dendritic transport
I D 200- 400 Post-synapse proteins, receptor complexes, proteins of the cytoplasm and membranes of the dendrite and spines Cytoskeleton, smooth reticulum, transport vesicles

Reverse (retrograde) transport
I R 100- 300 Spent lysosomes and mitochondria, growth and trophic factors, viruses. Multivesicular and multilamellar bodies, cytoskeleton, endosomes

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 so-called neurons participate in the implementation of transport processes in a neuron. “motor” molecules (Fig. xx).

1-3 Group. Kinesins

This group includes three types of kinesin proteins.

1. Group. Convection kinesin ( kinesin -I or KIF -5). It was identified in the nervous systems of cephalopods and mammals in 1985, and later in the cells of other animals, including lower eukaryotes. It is closely associated with microtubules and is one of the most important transport proteins of the cell, carrying out the transport of materials (cargo) along microtubules towards its plus end. With its help, mitochondria, lysosomes, endoplasmic reticulum cisterns, synaptic vesicles, as well as a number of non-membrane cell components (mRNA molecules, proteins and neurofilament fibrils) are transported in the processes of neurons.

The kinesin-1 molecule consists of two heavy and two light polypeptide chains. The heavy and light chains are each encoded by three genes. Light and heavy chains can combine in different combinations and are believed to be able to thus form different types of kinesin-I molecules, thereby transporting different components within the cell.

2.Group. Heterodimeric kinesin, (kinesin - II , kinesin-II, KIF – 3C).

It received its name due to the presence of three motor domains in the structure of the molecule. In nerve and sensory cells of vertebrates and invertebrates (for example: in vertebrate photoreceptors or in chemoreceptor cells of C. elegans), this protein is associated with the work of cilia and flagella, transporting large molecular complexes along their axonemal axis (IFT - intraflagellar transport) In nerve axons cells, it performs a transport function, moving synaptic vesicles and enzyme complexes (cholinesterase) involved in the functioning of synapses.

One of the forms of type II kinesin is the so-called. homodimeric kinesin (Osm 3, KIF-17) Found only in multicellular (metazoan) animals. Like heterodimeric kinesin II, it is an essential component of the cilia of chemoreceptive cells. In mammalian central nervous system neurons, this form of kinesin is involved in the transport of vesicles containing NMDA synaptic receptors along the dendrites. The involvement of homodimeric kinesin in IFT transport is debated.

3 Group. Monomeric kinesin (UNC -104, KIF -1A, Klp-53D, kinesin-73) This form of transport proteins has been found in the nervous system of C. elegans, where its mutant form caused paralysis of the transport of synaptic vesicles along the axons of motor neurons. The peculiarity of this transport molecule is that the predominant monomeric form of this protein is present, whereas other forms of kinesin (as noted above, are dimers or tetramers). Found in many animals (C. elegans - Unc104, Drosophila - Klp53 D, kinesin -73 mouse - KIF -1A, KIF -1B, humans - GAKIN), it takes part in the transport of synaptic vesicles, membrane proteins associated with the formation of cell contacts.

It has been shown that as a result of alternative splicing of the KIF-1B kinesin gene, two isoforms are formed: KIF-1 Bα, which is involved in transport along mitochondrial processes, and KIF-1Bβ, which transports synaptic vesicles to the axon terminal.

Once again, it must be emphasized that all forms of kinesins are involved in transport to the plus end of microtubules (anterograde, direct transport)

Tabditsa. Some molecular and functional characteristics of kinesins in nervous tissue (according to N. Hirokawa, 1997)

Molecule type Mol.weight Secondary structure Transport direction and speed Expression specificity Transported material
KIF-1A 192 monomer + end, 1.5 µm/sec neurospecific Synaptic vesicle precursors
KIF -1B 130 monomer + end, 0.66 µm/sec everywhere mitochondria
KIF 2 81 homodimer + end, 0.47 µm/sec Bubbles separating from syn precursors. bubbles
KIF3A 80 Heterodimer with KIF3B +end, 0.3 µm/sec Bubbles (90-180nm), from predecessors
KIF3B 85 Heterodimer with KIF3A +end, 0.3 µm/sec Common in neurons but expressed ubiquitously Bubbles (90-180nm), from synaptic vesicle precursors
KIF4 140 Homodimer, amino terminal motor domain + end, 0.2 µm/sec Ubiquitous, but weak in early development and in adult neurons Bubbles
KIF5
KIF 1C2 86 Homodimer, carboxyl-terminal motor domain - end, Neurospecific Multivesicular bodies, dendritic transport

4 Group Deneina.

These transport proteins are involved in transport along microtubules to its minus end (retrograde, reverse transport). They are present in many transport processes and cell movements, ranging from mitosis to neuroblast migration in the developing brain.

It has a rather complex structure, represented by many subunits (chains). These subunits interact with various denein-associated proteins, which, in turn, can determine the selective nature of the functions performed by denein in the cell. Thus, the protein lissencephalin-1 (Lis-1), being associated with denein, determines its role in mitosis and nuclear movement in cells of the developing brain, but not in the transport of organelles. Mutations or absence of this protein during the early development of the body (prenatal period) causes serious disturbances in the formation of the central nervous system and especially the cerebral cortex, ultimately leading to lissencephaly (a hereditary disease externally expressed in the underdevelopment or complete absence of gyri and sulci in the cerebral hemispheres).

5 Group. Myosins (myosin-Vs). This transport protein was first identified biochemically in the vertebrate brain as "myosin-like calmodulin binding protein". It differs from muscle myosin in the large, long hinge part of the molecule, which has an additional light chain and five molecules of calmodulin, a Ca+2 binding protein, attached to it.

Myosin V is widely involved in vertebrate and invertebrate animals in transport processes in nerve cells. It is mainly involved in the reverse transport of membrane vesicles, multivesicular bodies, waste organelles and their components, as well as neurotrophic and neurogrowth substances and, finally, viruses.

Kinesins provide transport in both directions (forward and reverse), but in all cases this transport goes to the “+” end of the microtubule. Deneins are involved in transport along microtubules to its “-” end. Myosins are transport proteins that are mainly involved in the reverse transport of membrane vesicles, multivesicular bodies, waste organelles and their components, as well as neurotrophic and neurogrowth substances and viruses. In addition, myosins also take part in the direct transport of cytoskeletal components along the processes and body of the neuron (for example, with its help short mobile microtubules move). Myosins play an important role in the growth of processes and their retraction during neuronal development and cell migration.

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.

Dendritic transport

For a long time, it was not possible to experimentally confirm the presence of transport in dendrites due to the significant volume of protein synthesis in the dendrites themselves. Only with the advent of the technique of intracellular injection of labeled precursors of protein synthesis and other cytoplasmic components, it was possible to show that there is transport in dendrites, as well as in axons. The speed of forward and reverse transport in dendrites is comparable to the speed of direct fast axonal transport.

Dendrites transport substances that are either not transported along axons or are transported in very limited quantities (for example: enzymes of mediator breakdown, components of postsynaptic thickenings, gangliosides (specific glycolipids of neuronal membranes), neurohormones and neurotrophic factors).

The presence of simultaneous forward and reverse transport in the processes of neurons creates the problem of their interaction with each other. The direction of transport flows in a neuron is believed to depend on the balance between forward and reverse transport, and this balance can be very different.

The state of the neuron cytoskeleton and motor complexes greatly affects the overall morphology of its processes. It has been shown that depending on which cytoskeletal components or motor molecules are activated or not, the shape, length and thickness of the processes change greatly.

As with direct transport, different components and substances are transported retrogradely in different neurons at different rates, and presumably in different ways.

Table. 4 Speeds of retrograde axonal transport of various molecules in the peripheral nervous system (modified from Reynolds et al., 2000)

Transported substance

Transport speed

Populations of neurons where transport is detected

NGF (neurogrowth factor)

2-5 mm/hour

10-13 mm/hour

Sympathetic neurons

Sensory neurons of the spinal ganglion

Dopamine β-hydroxylase enzyme

Sciatic nerve

Second messengers for phosphorylation of receptor tyrosine kinases

28-57 mm/hour

(8-16 µm/sec)

Sciatic nerve

Thus, neurons have a well-developed cytoskeleton and an associated effective system of direct and reverse transport of various materials and substances along the processes.



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.

Thirdly, 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 axon 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).

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 a special type of transport within the processes of a neuron, 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 various 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 part of the transported substances is released into the synaptic cleft and acts 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.

Membrane and cytoplasmic components that are formed in the biosynthetic apparatus of the soma and the proximal part of the dendrites must be distributed along the axon (their entry into the presynaptic structures of synapses is especially important) to compensate for the loss of elements that have been released or inactivated. However, many axons are too long for materials to move efficiently from the soma to the synaptic terminals by simple diffusion. This task is performed by a special mechanism - axonal transport.

There are several types. Membrane-enclosed organelles and mitochondria are transported at relatively high speeds via fast axonal transport. Substances dissolved in the cytoplasm (for example, proteins) move using slow axonal transport. In mammals, fast axonal transport has a speed of 400 mm/day, and slow axonal transport has a speed of about 1 mm/day. Synaptic vesicles can move by rapid axonal transport from the soma of a motor neuron in the human spinal cord to the neuromuscular junction of the foot in about 2.5 days. Let’s compare: delivery of many soluble proteins over the same distance occurs in approximately 3 g.

Axonal transport requires the expenditure of metabolic energy and the presence of intracellular Ca2+. Elements of the cytoskeleton (more precisely, microtubules) create a system of guide strands along which organelles surrounded by membranes move (Fig. 32.13). These organelles attach to microtubules in a manner similar to what occurs between the thick and thin filaments of skeletal muscle fibers; the movement of organelles along microtubules is triggered by Ca2+ ions.

Axonal transport occurs in two directions. Transport from the soma to the axonal terminals, called anterograde axonal transport (Fig. 32.14, a), replenishes the supply of synaptic vesicles and enzymes responsible for the synthesis of the neurotransmitter in the presynaptic terminals. Transport in the opposite direction - retrograde axonal transport (Fig. 32.14, b), returns empty synaptic vesicles to the soma, where these membrane structures are degraded by lysosomes.

Some viruses and toxins spread through peripheral nerves through axonal transport. Thus, the virus that can cause chickenpox (varicella-zoster virus) penetrates the cells of the spinal ganglia. There it remains in an inactive form, sometimes for many years, until the person’s immune status changes. Then the virus can be transported along sensory axons to the skin, and painful rashes appear in the dermatomes of the corresponding spinal nerves -



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