Axoplasmic transport
Encyclopedia
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...
, lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s, synaptic vesicle
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
s, protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, and other cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
parts (i.e. organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s) to and from a neuron's
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
cell body, through the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
of its axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
(the axoplasm
Axoplasm
Axoplasm is the cytoplasm within the axon of a neuron. Neural processes contain about 99.6% of the cell’s cytoplasm, and 99.7% of that is in the axons....
). Axons, which can be 1,000 or 10,000 times the length of the cell body, were originally thought to contain no ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
s or means of producing protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, and so were thought to rely on axoplasmic transport for all their protein needs. However, more recently translation of mRNA has been demonstrated in 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 lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
s.
Movement toward the cell body is called retrograde transport and movement toward the synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
is called anterograde transport.
Mechanism
The vast majority of axonal proteins are synthesized in the neuronal cell body and transported along axons. Axonal transport occurs throughout the life of a neuron and is essential to its growth and survival. MicrotubuleMicrotubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
s (made of tubulin
Tubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...
) run along the length of the axon and provide the main cytoskeletal "tracks" for transportation. The motor proteins kinesin
Kinesin
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule filaments, and are powered by the hydrolysis of ATP . The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular...
and dynein
Dynein
Dynein is a motor protein in cells which converts the chemical energy contained in ATP into the mechanical energy of movement. Dynein transports various cellular cargo by "walking" along cytoskeletal microtubules towards the minus-end of the microtubule, which is usually oriented towards the cell...
are mechanochemical enzymes that move cargoes in the anterograde (towards the axon tip) and retrograde (towards the cell body) directions, respectively. Motor proteins bind and transport several different cargoes including organelles such as mitochondria, cytoskeletal
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
s, and vesicle
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
s containing neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s.
Axonal transport can be divided into anterograde and retrograde categories, and further divided into fast and slow subtypes.
Fast and slow transport
Vesicular cargoes move relatively fast (50-400 mm/day) whereas transport of proteins takes much longer (moving at less than 8 mm/day). Fast axonal transport has been understood for decades but the mechanism of slow axonal transport has only recently been discovered as experimental techniques have improved. Fluorescent labeling techniques (e.g. fluorescence microscopyFluorescence microscope
A fluorescence microscope is an optical microscope used to study properties of organic or inorganic substances using the phenomena of fluorescence and phosphorescence instead of, or in addition to, reflection and absorption...
) have enabled direct visualization of transport in living neurons. (See also: Anterograde tracing
Anterograde tracing
In neuroscience, anterograde tracing is a research method which is used to trace axonal projections from their source In neuroscience, anterograde tracing is a research method which is used to trace axonal projections from their source In neuroscience, anterograde tracing is a research method which...
.)
Recent studies have revealed that the movement of individual "slow" cargoes is actually rapid but unlike fast cargoes, they pause frequently, making the overall transit rate much slower. The mechanism is known as the "Stop and Go" model of slow axonal transport. An analogy is the difference in transport rates between local and express subway trains. Though both types of train travel at similar velocities between stations, the local train takes much longer to reach the end of the line because it stops at every station whereas the express makes only a few stops on the way.
Anterograde transport
Anterograde (also called "orthograde") transport is movement of molecules/organelles from the cell body to the synapse.The rapid movement of individual cargoes (in transport vesicles) of both fast and slow components along the microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
indicates that all anterograde transport is mediated by kinesin
Kinesin
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule filaments, and are powered by the hydrolysis of ATP . The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular...
s. Several kinesins have been implicated in slow transport, though the mechanism for generating the "pauses" in the transit of slow component cargoes is still unknown.
There are two classes of slow anterograde transport: slow component a (SCa) that carries mainly microtubules and neurofilament
Neurofilament
Neurofilaments are the 10 nanometer intermediate filaments found specifically in neurons. They are a major component of the cell's cytoskeleton, and provide support for normal axonal radial growth...
s at 0.1-1 millimeter per day, and slow component b (SCb) that carries over 200 diverse proteins and actin at a rate of up to six millimeters a day. The slow component b, which also carries actin, are transported at a rate of 2-3 mm/day in retinal cell axons.
Retrograde transport
Retrograde transport, which is mediated by dynein, sends chemical messages and endocytosisEndocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
products headed to endolysosomes from the axon back to the cell. Fast retrograde transport can cover 100-200 millimeters per day.
Consequences of interruption
Since the axon depends on axoplasmic transport for vital proteins and materials, injury such as diffuse axonal injuryDiffuse axonal injury
Diffuse axonal injury is one of the most common and devastating types of traumatic brain injury, meaning that damage occurs over a more widespread area than in focal brain injury. DAI, which refers to extensive lesions in white matter tracts, is one of the major causes of unconsciousness and...
that interrupts the transport will cause the distal axon to degenerate in a process called Wallerian degeneration
Wallerian degeneration
Wallerian degeneration is a process that results when a nerve fiber is cut or crushed, in which the part of the axon separated from the neuron's cell body degenerates distal to the injury. This is also known as anterograde degeneration, or orthograde degeneration...
. Dysfunctional axonal transport is also linked to neurodegenerative disease such as Alzheimer's.
Cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
drugs that interfere with cancerous growth by altering microtubules (which are necessary for cell division
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
) damage nerves because the microtubules are necessary for axonal transport.