Abstract
Axons are long slender cylindrical projections of neurons that enable these cells to communicate directly with other cells in the body over long distances, up to a meter or more in large animals. Remarkably, however, most axonal components originate in the nerve cell body, at one end of the axon, and must be shipped out along the axon by mechanisms of intracellular motility. In addition, signals from the axon and its environment must be conveyed back to the nerve cell body to modulate the nature and composition of the outbound traffic. The outward movement from the cell body toward the axon tip is called anterograde transport and the movement in the opposite direction, back toward the cell body, is called retrograde transport. This bidirectional transport, known collectively as axonal transport, is not fundamentally different from the pathways of macromolecular and membrane traffic found in other parts of the neuron, or indeed in any eukaryotic cell, but it is unique for the volume and scale of the traffic required to maintain these long processes.
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Video 1
Axonal transport of membranous organelles in the squid giant axon revealed by video-enhanced light microscopy. This movie is a digitization of a video clip obtained in the early 1980s using video-enhanced contrast differential interference contrast (VEC-DIC) microscopy, originally recorded with an analog video camera. The movie shows organelle movement in axoplasm extruded from a squid giant axon. Note the movement of many tiny diffraction-limited vesicles along linear tracks, which are microtubules. The large sausage-shaped organelles are mitochondria, which move in an intermittent manner. The long axis of the axon is orientated approximately diagonally in this movie, from lower left to upper right, but the microtubule tracks are a bit disorganized in this preparation because of compression of the axoplasm during the extrusion process. This movie is provided courtesy of Susan Gilbert and Roger Sloboda. The width of the field of view is 25.6 μm. The methods used to obtain these movies are described in two back-to-back papers in Science in 1980 (Allen et al. 1982; Brady et al. 1982). Similar movies were published by Allen et al. 1990 and Weiss et al. 1990 in Cell Motility and the Cytoskeleton 17:356–372, 1990 (Tracks 20 %26 21, Video Supplement 2: Microtubule-Based Motility, ed. J.M. Sanger %26 J.W. Sanger)
Video 2
Axonal transport of neurosecretory vesicles in the nerve of a fly larva revealed by fluorescence microscopy. This is a time-lapse video of large (“dense-core”) neurosecretory vesicles in the segmental nerve of a third instar Drosophila (fruit fly) larva, engineered to express a fluorescent neuropeptide (atrial natriuretic factor fused to green fluorescent protein; ANF-GFP) in neurons. Time-lapse imaging was performed with a spinning disk confocal microscope at 2 frames/s. The vesicles move bidirectionally at a velocity of about 1 μm/s. The nerve contains about 70 axons, but the number in this optical section is likely to be about 5–15 (Reproduced from Barkus et al. 2008)
Video 3
Axonal transport of synaptobrevin, an integral membrane protein component of synaptic vesicles. This is a time-lapse video of synaptobrevin tagged with green fluorescent protein in motor axons of a fly larval segmental nerve, which contains several axons. The movie was acquired with a spinning disk confocal microscope at 1 frame/s. The elapsed time (minutes:seconds) is shown in the lower right. Anterograde is toward the right and retrograde is toward the left. Note the fast bidirectional movement of the punctate structures, which are the transported vesicles (Reproduced from Horiuchi et al. 2005)
Video 4
Axonal transport of neurofilament polymers in a cultured nerve cell. Neurofilament movement in a cultured nerve cell expressing a green fluorescent neurofilament fusion protein, which coassembles with the endogenous neurofilament proteins to form green fluorescent neurofilaments. At just 10 nm in diameter, the filaments are well below the diffraction-limited resolution of light microscopy, but they are visible in these axons because they are relatively sparsely distributed. In mature axons in vivo, neurofilaments are often very numerous, and such imaging would not be possible. The outline of the axon and its branches is indicated in green. The polymers exhibit bouts of rapid movement in both anterograde and retrograde directions interrupted by pauses of varying duration. When pausing, the filaments also exhibit complex jiggling and folding behaviors. Proximal is left, distal is right. Time compression = 50:1 (Reproduced from Wang and Brown 2010)
Video 5
The bidirectional transport of neurofilaments in axons of a cultured nerve cell. Time-lapse imaging of neurofilaments in the axon of a cultured nerve cell expressing neurofilament protein tagged with green fluorescent protein. Note that some neurofilaments move anterogradely and others move retrogradely. Proximal is left and distal is right. Time compression = 50:1 (Reproduced from Wang and Brown 2010)
Video 6
The bidirectional transport of mitochondria in Drosophila larval nerve. Time-lapse imaging of a segmental nerve in a fly larva expressing green fluorescent protein targeted to mitochondria. Note that the nerve contains multiple axons. To visualize mitochondrial movement, the fluorescence was bleached in a central section of the nerve and then the movement of fluorescent mitochondria into the bleached zone from the flanking unbleached regions was imaged at 1 frame/s with a confocal microscope. Proximal is left and distal is right. Time compression = 15:1. Note that anterogradely moving mitochondria predominate, but some mitochondria move retrogradely (Reproduced from Pilling et al. 2006)
Video 7
The bidirectional transport of mitochondria in a living mouse. Time-lapse imaging of mitochondrial movement in a transgenic mouse expressing cyan fluorescent protein targeted to mitochondria. The movie shows two axons of an intercostal nerve, which innervates the triangularis sterni muscles of the rib cage. A node of Ranvier is present in the upper axon. The majority of mitochondria are immobile, but a fraction moves quickly (about 1–1.5 μm/s) in either anterograde or retrograde directions. At nodes of Ranvier transported mitochondria often slow down and sometimes pause, thereby positioning these organelles where they are most needed to support the energy demands of the axon during electrical activity. Proximal is left, distal is right. Time is indicated in minutes:seconds. This represents the first direct imaging of axonal transport in a living mouse (Reproduced from Misgeld et al. 2007)
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Brown, A. (2015). Axonal Transport. In: Pfaff, D., Volkow, N. (eds) Neuroscience in the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6434-1_14-3
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DOI: https://doi.org/10.1007/978-1-4614-6434-1_14-3
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