Essential materials are packaged within vesicles that travel along the cytoskeleton in the interior of the axon at rates of up to 40 mm/day.
Transport of materials from cell body to nerve terminals is called anterograde axonal transport, and from nerve terminals to the cell body is retrograde axonal transport.
Retrograde transport informs the neuronal nucleus about the state of the nerve endings and the integrity of synaptic function. The neurotubular system also carries unwanted denatured or misfolded proteins back towards the perinuclear area (centrosome).
It takes ~2.5 days for materials synthesised in neuronal cell bodies in the spinal cord to reach axon terminals in the human foot, around one metre distant, and a further ~2.5 days for a retrograde chemical message to do the return journey. This slow process informs the neuronal nucleus about the state of the nerve endings and the integrity of synaptic function.
How does the cell nucleus communicate with the distant parts of the neurone?
Fast axonal transport carries materials between the cell body and the terminals at rates of up to 40 mm/day.
Vesicles are often used to package these materials. It takes ~2.5 days for materials synthesised in the Nissl Substance (ribosomes) of neuronal cell bodies in the spinal cord to reach axon terminals in the human foot, one metre distant, and a further ~2.5 days for a retrograde chemical message to do the return journey.
This slow return process informs the neuronal nucleus about the state of the nerve endings and the integrity of synaptic function.
All animal cells contain a cytoskeleton consisting of microtubules that are organised by and anchored to the centrosome, situated near the nucleus of the cell. They act as guides for the transport of materials within the cell. In nerve cells the microtubules are called neurotubules and pass down the cytoplasm in the centre of the axon as far as the axon terminal.
Axoplasmic Transport is the transport of chemicals, vesicles and cell organelles along the interior of the axon.
The cytoplasm of axons contains neurotubules which are the transport system (like railway tracks) along which packages containing essential materials are transported through the axoplasm.
Fast and Slow Axoplasmic Flow.
'Fast axonal transport' is the speed of transport of materials down the axon at around 100 mm/day (extremely slow compared to 100 m/sec for the action potential in the cell membrane). Vesicles are transported by the fast mechanism.
'Slow axonal transport' is much slower - around 1 - 6 mm/day and is used to transport neurofilaments as well as other proteins.
Two classes of proteins - kinesins and dyneins act as molecular motors that carry organelles and other materials along the track - the neurotubules. The kinesins transport substances in an anterograde direction (from cell body to axon terminal), and dyneins are responsible for retrograde transport (from axon terminal to cell body).
Image source: Wikipedia Commons
Rat brain cells grown in tissue culture and stained, in green, with an antibody to neurofilament subunit NF-L, which reveals a large neuron. Neurofilaments are structural proteins, responsible for maintaining axonal diameter and other features of the neurone.
Proteins are synthesised within the Nissl substance of cell bodies, and are transported down the axon in an anterograde direction.
In addition to the enzymes, neurotransmitters and structural proteins, cell organelles need to be replaced regularly, and anterograde axonal transport is essential for the delivery of materials the axon and its terminals.
Materials are transported within vesicles: dense-cored vesicles carry peptides along the length of the axoplasm.
Neurofilaments provide the structural support for the neuronal cytoskeleton, including dendrites and axons, where determine axon diameter.
Neurofilaments are synthesised in the neuronal cell body; during nerve regeneration their rate of synthesis is increased as they are needed to extend the axon and increase the diameter of the regenerated axon terminals.
Glia do not contain neurofilaments.
What materials are transported from the terminal to the nucleus?
Retrograde transport mechanisms carry some vesicular material that is being returned to the cell body for recycling. Denatured or misfolded proteins are also carried.
At the pre-synaptic membrane of the synaptic bouton, clathrin-coated vesicles are believed to be involved in endocytosis - the formation of vesicles that sample the extracellular fluid within the synapse.
Chemical messages, including some released by the postsynaptic cell are retrogradely transported and are thought to be a signal that informs the neuronal cell body that its nerve endings are in close contact with the target cells.
Growth factors such as neurotrophins (such as Nerve Growth Factor, Neurotrophin-1) are believed to be passed from the post-synaptic cell into the presynaptic terminals, and are transported back to the neuronal cell body.
These chemical messages inform the nucleus of the integrity and effectiveness of distant synaptic contacts.
Neurotrophins are a group of small proteins that appear to be involved in the development and maintenance of synapses.
Nerve Growth Factor (NGF; NT-1) and Brain-Derived Neurotrophic Factor (BDNF) are examples of neurotrophins.
Axonal Transport in Neurodegenerative Disorders
In a number of neurodegenerative diseases there are structural changes in neurones including inclusion bodies and neurofibrillary tangles; it is suggested that these neuronal changes interfere with internal communication within neurones because of disruption of axoplasmic transport.
Image source: www.studyblue.com
Normal microtubules guide the movement of vesicles down the axoplasm, and are stabilised by the presence of a protein called tau.
In Alzheimer's disease an abnormally large number of additional phosphate molecules are found to be attached to tau, and allows neurotubules to disintegrate, and at the same time hyperphosphorylated tau joins with other filaments to form a sort of mesh that interferes with the transport of materials.
This leads to a total disruption of the internal communication within the nerve cell, and a failure of axonal transport.
Internal communication between the nucleus and axon terminals fail to be coordinated. Failure of neuronal function can initiate the death of neurones, a feature of many neurodegenerative diseases.
Summary of processes and some important molecules involved in axonal transport