Axoplasmic transport, also called axonal transport, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other cell parts (i.e. organelles) to and from a neuron's cell body, through the cytoplasm of its axon (the axoplasm). Axons, which can be 1,000 or 10,000 times the length of the cell body, were originally thought to contain no ribosomes or means of producing proteins, and so were thought to rely on axoplasmic transport for all their protein needs.[1][2] However, more recently translation of mRNA has been demonstrated in axons.[3][4] 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.[5]
Movement toward the cell body is called retrograde transport and movement toward the synapse is called anterograde transport.[1][6][7]
Contents |
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. Microtubules (made of tubulin) run along the length of the axon and provide the main cytoskeletal "tracks" for transportation. The motor proteins kinesin and dynein 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 polymers, and vesicles containing neurotransmitters.[1]
Axonal transport can be divided into anterograde and retrograde categories, and further divided into fast and slow subtypes.
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.[8] Fluorescent labeling techniques (e.g. fluorescence microscopy) have enabled direct visualization of transport in living neurons. (See also: Anterograde tracing.)
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.[9][10] 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 (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[7] indicates that all anterograde transport is mediated by kinesins. Several kinesins have been implicated in slow transport[8], 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 neurofilaments 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.[8] The slow component b, which also carries actin, are transported at a rate of 2-3 mm/day in retinal cell axons.
An example of the use of anterograde transport is the Herpes simplex virus (HSV). This virus reactivates from latency in the neurons of dorsal root ganglia (DRG) and is subsequently transported anterogradely along the axon to be shed at the skin or mucosa. [11]
Retrograde transport, which is mediated by dynein, sends chemical messages and endocytosis products headed to endolysosomes from the axon back to the cell.[5] Fast retrograde transport can cover 100-200 millimeters per day.[5]
Fast retrograde transport returns used synaptic vesicles and other materials to the soma and informs the soma of conditions at the axon terminals. Some pathogens exploit this process to invade the nervous system. They enter the distal tips on an axon and travel to the soma by retrograde transport. Examples include tetanus toxin and the herpes simplex, rabies, and polio viruses. In such infections, the delay between infection and the onset of symptoms corresponds to the time needed for the pathogens to reach the somas. [12]
Since the axon depends on axoplasmic transport for vital proteins and materials, injury such as diffuse axonal injury that interrupts the transport will cause the distal axon to degenerate in a process called Wallerian degeneration. Dysfunctional axonal transport is also linked to neurodegenerative disease such as Alzheimer's.[8]
Cancer drugs that interfere with cancerous growth by altering microtubules (which are necessary for cell division) damage nerves because the microtubules are necessary for axonal transport.[1]