Axonal Transport and the Neuronal Cytoskeleton

Abstract

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.