Axonal Transport and the Neuronal Cytoskeleton


The neuronal cytoskeleton is a system of highly organised polymers that provide architectural support for axons and dendrites and also provide railways for the transport of various classes of cytoplasmic constituents. Molecular motor proteins use the energy derived from adenosine triphosphate hydrolysis for the transport of organelles along the cytoskeletal polymers and for the transport of the polymers themselves. Axons can traverse exceeding long distances in the body, and hence require sophisticated mechanisms of axonal transport in both anterograde and retrograde directions.

Key Concepts

  • The neuronal cytoskeleton is composed of three classes of polymers (microtubules, microfilaments and neurofilaments) together with a host of accessory proteins that organise and regulate these polymers.
  • The movement of cytoplasmic constituents within the axon is termed axonal transport, and this movement has been the topic of intense study for over 50 years.
  • Microtubules are organised into distinct patterns of polarity orientation in axons and dendrites, with almost all axonal microtubules organised with their plus ends directed outward from the cell body, whereas dendritic microtubules are organised with roughly equal numbers having each orientation.
  • Molecular motor proteins hydrolyse ATP in order to move along microtubules or microfilaments, with such movements serving to transport organelles but also serving to organise the cytoskeletal elements themselves.
  • Cytoplasmic dynein and kinesins are the molecular motors that move along microtubules, while myosins are the molecular motors that move along microfilaments.
  • Fast axonal transport is the movement of organelles along microtubules in the axon, with kinesins moving organelles anterogradely and cytoplasmic dynein moving organelles retrogradely.
  • Dendritic transport also occurs, using much the same principles as axonal transport, but on a microtubule array with a different pattern of organisation than the axon.
  • Slow axonal transport is the movement of the proteins that comprise the cytoskeleton, their associated proteins, and also cytosolic proteins.
  • Knowledge of the mechanisms of slow axonal transport of cytoskeletal proteins is key to understanding how the cytoskeletal arrays themselves are organised in the neuron.
  • Progress on understanding the neuronal cytoskeleton and axonal transport has been instrumental in improving understanding of many neurodegenerative and neurodevelopmental disorders.

Keywords: axon; dendrite; neuron; axonal transport; microtubule; microfilament; motor protein; neurofilament

Figure 1. Structure of cytoskeletal polymers and molecular motors. One example of each type of motor is shown.
Figure 2. Overall neuronal cytoskeletal structure and some of the players that are involved in neuronal transport.
Figure 3. Microtubule polarity orientation in axon versus dendrites of a vertebrate neuron. In the axon, nearly all microtubules have their plus ends directed outward, away from the cell body of the neuron, while in the dendrites the microtubules are of mixed polarity, that is roughly half the microtubules have their plus ends directed outward while roughly half the microtubules have their minus ends directed outward. Note: It has been reported in some invertebrates that microtubules in dendrites are predominantly oriented with minus ends outward.
Figure 4. Fast axonal transport is the movement of vesicular organelles and their associated proteins along microtubules in the axon. Vesicular organelle cargoes move anterogradely towards the plus end of microtubules, via kinesins, and retrogradely towards the minus end of microtubules, via cytoplasmic dynein. Motors are complex and a number of different ones can participate to regulate and fine tune these various movements.
Figure 5. Slow axonal transport is a term used to encompass the movement of cytoskeletal and cytoskeletal‐associated proteins as well as cytosolic proteins in the axon. The organisation of microtubules, microfilaments and neurofilaments in the axon is a direct result of slow transport mechanisms. In developing neurons, microtubules originate at the centrosome, are released from the centrosome, and are then transported into the axon. In older axons, new microtubules can arise via severing of older microtubules or by local nucleation events. Microtubules move within the axon chiefly by cytoplasmic dynein moving them with plus‐end‐leading; this directionality drives correctly oriented microtubules down the axon and incorrectly oriented microtubules back to the cell body. Neurofilaments move similarly to vesicular cargo in fast axonal transport, using kinesin and cytoplasmic dynein for anterograde and retrograde movements, respectively. Transport of actin is poorly understood but may involve the movement of microfilaments via myosin and/or movement via bursts of anterogradely favoured assembly in a process manifested in live imaging as actin trails. Cytosolic proteins cluster together and undergo intermittent bouts of transport on microtubules via kinesin and cytoplasmic dynein. Motors are complex and a number of different ones can participate to regulate and fine tune these various movements.


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Further Reading

Bodakuntla S, Jijumon AS, Villablanca C, Gonzalez‐Billault C and Janke C (2019) Microtubule‐associated proteins: structuring the cytoskeleton. Trends in Cell Biology 29 (10): 804–819. DOI: 10.1016/j.tcb.2019.07.004.

Nirschl JJ, Ghiretti AE and Holzbaur ELF (2017) The impact of cytoskeletal organization on the local regulation of neuronal transport. Nature Reviews Neuroscience 18 (10): 585–597.

Sleigh JN, Rossor AM, Fellows AD, Tosolini AP and Schiavo G (2018) Axonal transport and neurological disease. Nature Reviews Neurology 15: 691–703. DOI: 10.1038/s41582‐019‐0257‐2.

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Muralidharan, H, and Baas, PW(Mar 2020) Axonal Transport and the Neuronal Cytoskeleton. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000082.pub3]