Axoplasm | |
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Details | |
Part of | Axon of a nerve |
System | Nervous system |
Identifiers | |
Latin | axoplasma |
TH | H2.00.06.1.00019 |
Anatomical terminology |
Axoplasm is the cytoplasm within the axon of a neuron (nerve cell). For some neuronal types this can be more than 99% of the total cytoplasm. [1]
Axoplasm has a different composition of organelles and other materials than that found in the neuron's cell body (soma) or dendrites. In axonal transport (also known as axoplasmic transport) materials are carried through the axoplasm to or from the soma.
The electrical resistance of the axoplasm, called axoplasmic resistance, is one aspect of a neuron's cable properties, because it affects the rate of travel of an action potential down an axon. If the axoplasm contains many molecules that are not electrically conductive, it will slow the travel of the potential because it will cause more ions to flow across the axolemma (the axon's membrane) than through the axoplasm.
Axoplasm is composed of various organelles and cytoskeletal elements. The axoplasm contains a high concentration of elongated mitochondria, microfilaments, and microtubules. [2] Axoplasm lacks much of the cellular machinery (ribosomes and nucleus) required to transcribe and translate complex proteins. As a result, most enzymes and large proteins are transported from the soma through the axoplasm. Axonal transport occurs either by fast or slow transport. Fast transport involves vesicular contents (like organelles) being moved along microtubules by motor proteins at a rate of 50–400mm per day. [3] Slow axoplasmic transport involves the movement of cytosolic soluble proteins and cytoskeletal elements at a much slower rate of 0.02-0.1mm/d. The precise mechanism of slow axonal transport remains unknown but recent studies have proposed that it may function by means of transient association with the fast axonal transport vesicles. [4] Though axonal transport is responsible for most organelles and complex proteins present in the axoplasm, recent studies have shown that some translation does occur in axoplasm. This axoplasmic translation is possible due to the presence of localized translationally silent mRNA and ribonuclear protein complexes. [5]
Axoplasm is integral to the overall function of neurons in propagating action potential through the axon. The amount of axoplasm in the axon is important to the cable like properties of the axon in cable theory. In regards to cable theory, the axoplasmic content determines the resistance of the axon to a potential change. The composing cytoskeletal elements of axoplasm, neural filaments, and microtubules provide the framework for axonal transport which allows for neurotransmitters to reach the synapse. Furthermore, axoplasm contains the pre-synaptic vesicles of neurotransmitter which are eventually released into the synaptic cleft.
Axoplasm contains both the mRNA and ribonuclearprotein required for axonal protein synthesis. Axonal protein synthesis has been shown to be integral in both neural regeneration and in localized responses to axon damage. [5] When an axon is damaged, both axonal translation and retrograde axonal transport are required to propagate a signal to the soma that the cell is damaged. [5]
Axoplasm was not a main focus for neurological research until after many years of learning of the functions and properties of squid giant axons. Axons in general were very difficult to study due to their narrow structure and in close proximity to glial cells. [6] To solve this problem squid axons were used as an animal model due to the relatively vast sized axons compared to humans or other mammals. [7] These axons were mainly studied to understand action potential, and axoplasm was soon understood to be important in membrane potential. [8] The axoplasm was at first just thought to be very similar to cytoplasm, but axoplasm plays an important role in transference of nutrients and electrical potential that is generated by neurons. [9]
It actually proves quite difficult to isolate axons from the myelin that surrounds it, [10] so the squid giant axon is the focus for many studies that touch on axoplasm. As more knowledge formed from studying the signalling that occurs in neurons, transfer of nutrients and materials became an important topic to research. The mechanisms for the proliferation and sustained electrical potentials were affected by the fast axonal transport system. The fast axonal transport system uses the axoplasm for movement, and contains many non-conductive molecules that change the rate of these electrical potentials across the axon, [11] but the opposite influence does not occur. The fast axonal transport system is able to function without an axolemma, implying that the electrical potential does not influence the transport of materials through the axon. [12] This understanding of the relationship of axoplasm regarding transport and electrical potential is critical in the understanding of the overall brain functions.
With this knowledge, axoplasm has become a model for studying varying cell signaling and functions for the research of neurological diseases like Alzheimer's, [13] and Huntington's. [14] Fast axonal transport is a crucial mechanism when examining these diseases and determining how a lack of materials and nutrients can influence the progression of neurological disorders.
An axon or nerve fiber is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.
Myelin is a lipid-rich material that surrounds nerve cell axons to insulate them and increase the rate at which electrical impulses pass along the axon. The myelinated axon can be likened to an electrical wire with insulating material (myelin) around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, myelin ensheaths the axon segmentally: in general, each axon is encased in multiple long sheaths with short gaps between, called nodes of Ranvier. At the nodes of Ranvier, which are approximately one thousandth of a mm (one micrometre in length, the axon's membrane is bare of myelin.
A neuron, neurone, or nerve cell is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the brain and spinal cord and help to receive and conduct impulses. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap.
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components: microfilaments, intermediate filaments, and microtubules, and these are all capable of rapid growth and or disassembly depending on the cell's requirements.
Dyneins are a family of cytoskeletal motor proteins that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargos, provides forces and displacements important in mitosis, and drives the beat of eukaryotic cilia and flagella. All of these functions rely on dynein's ability to move towards the minus-end of the microtubules, known as retrograde transport; thus, they are called "minus-end directed motors". In contrast, most kinesin motor proteins move toward the microtubules' plus-end, in what is called anterograde transport.
Nodes of Ranvier, also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated axonal domains that are highly enriched in sodium and potassium ion channels complexed with cell adhesion molecules, allowing them to participate in the exchange of ions required to regenerate the action potential. Nerve conduction in myelinated axons is referred to as saltatory conduction due to the manner in which the action potential seems to "jump" from one node to the next along the axon. This results in faster conduction of the action potential. The nodes of Ranvier are present in both the peripheral and central nervous systems.
Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.
Neurofilaments (NF) are classed as type IV intermediate filaments found in the cytoplasm of neurons. They are protein polymers measuring 10 nm in diameter and many micrometers in length. Together with microtubules (~25 nm) and microfilaments (7 nm), they form the neuronal cytoskeleton. They are believed to function primarily to provide structural support for axons and to regulate axon diameter, which influences nerve conduction velocity. The proteins that form neurofilaments are members of the intermediate filament protein family, which is divided into six types based on their gene organization and protein structure. Types I and II are the keratins which are expressed in epithelia. Type III contains the proteins vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP). Type IV consists of the neurofilament proteins NF-L, NF-M, NF-H and α-internexin. Type V consists of the nuclear lamins, and type VI consists of the protein nestin. The type IV intermediate filament genes all share two unique introns not found in other intermediate filament gene sequences, suggesting a common evolutionary origin from one primitive type IV gene.
In cellular neuroscience, the soma, neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. Although it is often used to refer to neurons, it can also refer to other cell types as well, including astrocytes, oligodendrocytes, and microglia. The part of the soma without the nucleus is called perikaryon.
Axonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytoplasm of its axon called the axoplasm. Since some axons are on the order of meters long, neurons cannot rely on diffusion to carry products of the nucleus and organelles to the ends of their axons. Axonal transport is also responsible for moving molecules destined for degradation from the axon back to the cell body, where they are broken down by lysosomes.
Motor proteins are a class of molecular motors that can move along the cytoskeleton of cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump.
A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope. He first described the growth cone based on fixed cells as "a concentration of protoplasm of conical form, endowed with amoeboid movements". Growth cones are situated on the tips of neurites, either dendrites or axons, of the nerve cell. The sensory, motor, integrative, and adaptive functions of growing axons and dendrites are all contained within this specialized structure.
Huntingtin-associated protein 1 (HAP1) is a protein which in humans is encoded by the HAP1 gene. This protein was found to bind to the mutant huntingtin protein (mHtt) in proportion to the number of glutamines present in the glutamine repeat region.
In cellular neuroscience, chromatolysis is the dissolution of the Nissl bodies in the cell body of a neuron. It is an induced response of the cell usually triggered by axotomy, ischemia, toxicity to the cell, cell exhaustion, virus infections, and hibernation in lower vertebrates. Neuronal recovery through regeneration can occur after chromatolysis, but most often it is a precursor of apoptosis. The event of chromatolysis is also characterized by a prominent migration of the nucleus towards the periphery of the cell and an increase in the size of the nucleolus, nucleus, and cell body. The term "chromatolysis" was initially used in the 1940s to describe the observed form of cell death characterized by the gradual disintegration of nuclear components; a process which is now called apoptosis. Chromatolysis is still used as a term to distinguish the particular apoptotic process in the neuronal cells, where Nissl substance disintegrates.
Axon terminals are distal terminations of the branches of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell that conducts electrical impulses called action potentials away from the neuron's cell body to transmit those impulses to other neurons, muscle cells, or glands. Most presynaptic terminals in the central nervous system are formed along the axons, not at their ends.
Kinesin-like protein KIF1A, also known as axonal transporter of synaptic vesicles or microtubule-based motor KIF1A, is a protein that in humans is encoded by the KIF1A gene.
Kinesin-like protein KIF11 is a molecular motor protein that is essential in mitosis. In humans it is coded for by the gene KIF11. Kinesin-like protein KIF11 is a member of the kinesin superfamily, which are nanomotors that move along microtubule tracks in the cell. Named from studies in the early days of discovery, it is also known as Kinesin-5, or as BimC, Eg5 or N-2, based on the founding members of this kinesin family.
Intracellular transport is the movement of vesicles and substances within a cell. Intracellular transport is required for maintaining homeostasis within the cell by responding to physiological signals. Proteins synthesized in the cytosol are distributed to their respective organelles, according to their specific amino acid’s sorting sequence. Eukaryotic cells transport packets of components to particular intracellular locations by attaching them to molecular motors that haul them along microtubules and actin filaments. Since intracellular transport heavily relies on microtubules for movement, the components of the cytoskeleton play a vital role in trafficking vesicles between organelles and the plasma membrane by providing mechanical support. Through this pathway, it is possible to facilitate the movement of essential molecules such as membrane‐bounded vesicles and organelles, mRNA, and chromosomes.
Neurotubules are microtubules found in neurons in nervous tissues. Along with neurofilaments and microfilaments, they form the cytoskeleton of neurons. Neurotubules are undivided hollow cylinders that are made up of tubulin protein polymers and arrays parallel to the plasma membrane in neurons. Neurotubules have an outer diameter of about 23 nm and an inner diameter, also known as the central core, of about 12 nm. The wall of a neurotubule is about 5 nm in width. There is a non-opaque clear zone surrounding the neurotubule and it is about 40 nm in diameter. Like microtubules, neurotubules are greatly dynamic and their length can be adjusted by polymerization and depolymerization of tubulin.
Casper Hoogenraad is a Dutch Cell Biologist who specializes in molecular neuroscience. The focus of his research is the basic molecular and cellular mechanisms that regulate the development and function of the brain. As of January 2020, he serves as Vice President of Neuroscience at Genentech Research and Early Development.