Axoplasmic Transport

The axoplasm is not static but, rather, participates in a state of dynamic flow. There are at least two reasons for this. One is the necessity for maintenance of the

Figure 4 Electron micrographs of monkey cortical tissue. Two axons (AX) have been anterogradely filled with tracer transported from a distant injection site. Several other unlabeled axons occur in the same field (asterisks). M, myelin.

cytoskeleton, plasmalemma, synaptic apparatus, and other organelle components. Since little or no protein synthesis takes place within the axon proper, materials synthesized within the cell body must be transported along the full length of the axon. A second, less understood requirement relates to the encoding and regulatory functions of the axon, whereby conditions at its distal end are signaled back to the cell body.

Axoplasmic Transport

Figure 5 Photomicrographs of two corticocortical axon arbors anterogradely filled with tracer (BDA) transported from a distant injection site. Both arbors are about the same size. One (A, B) has very large terminal specializations. The other (C, D) has delicate beaded and stalked endings and is more typical. B is higher magnification of A. D is higher magnification of C. Arrows point to corresponding features.

Figure 5 Photomicrographs of two corticocortical axon arbors anterogradely filled with tracer (BDA) transported from a distant injection site. Both arbors are about the same size. One (A, B) has very large terminal specializations. The other (C, D) has delicate beaded and stalked endings and is more typical. B is higher magnification of A. D is higher magnification of C. Arrows point to corresponding features.

Axon transport is a complex process that operates in both the anterograde (toward the distal end with terminal arbors) and retrograde (toward the cell body) directions (Fig. 6). There are several subcomponents that require many different mechanisms. The main distinction is between fast and slow transport. Fast transport operates in both the anterograde and retro grade directions and comprises several rate classes. These may reflect differences in transport mechanisms and/or the sieving action of the cytoskeletal meshwork on organelles of different sizes. Small vesicles and neurotransmitter molecules are conveyed at the fastest velocity (200-400 mm/day), mitochondria at 50-100 mm/day, and various metabolic enzymes at

28 mm/day. Microtubules and neurofilaments migrate by slow transport, which proceeds at less than 5 mm/day.

1. Fast Transport

Early work on axon transport took place in the 1940s, in part motivated by interest in axon regeneration during World War II. The phenomenon was simply but convincingly demonstrated by the accumulation of an irregular bulge of material proximal to a ligature placed around a single axon. When the constriction was removed, the accumulated material continued down the axon at a rate of about 1.0 mm/day. Fast transport (i.e., at rates of 50-400 mm/day) was demonstrated several decades later by the uptake of radioactively labeled amino acids by the cell soma. The label is incorporated into proteins and transported down the axon, where the pulse of radioactive material is then sampled by either autoradiography or scintillation counting.

Recently, investigations of axon transport have shifted from elucidation of what materials are transported and at what rate to unraveling the underlying mechanisms. Indirect evidence had already suggested the importance of microtubules. For example, agents such as colchicine that disrupt microtubules, also interfere with transport. More direct evidence of the role of microtubules in fast transport was provided by studies using the compound b, briminodiproprioni-

trile, which causes microtubules to segregate from neurofilaments and form several bundles in the center of the axon. Electron microscopy and autoradiography show a clear association of mitochondria and other rapidly transported elements with the central clusters of microtubules. Finally, enhanced videomicroscopy of microtubules extruded from axoplasm indicates that these can transport organelles and vesicles.

In the transport process, microtubules operate in concert with several ''molecular motors'' (Fig. 7). The energy-transducing protein, kinesin transports organelles anterogradely along microtubules. Dynein, another microtuble-associated ATPase, is implicated in retrograde transport. The role of kinesin has been established experimentally. Injection of antisense oligonucleotides suppresses kinesin heavy-chain expression and concurrently results in abnormal accumulation of protein within the cell body. Additionally, kinesin heavy-chain mutations produce various disruptions in action potential propagation and neurotransmitter release.

Recent studies have identified additional carboxy-terminal-type proteins within the kinesin superfamily that participate in the transport of specific organelles at specific velocities. Most of these putative motors have been characterized by molecular cell biological approaches, such as cloning and sequencing of the genes encoding these proteins, expression and purification of the proteins using the baculovirus Sf9 cell system, observation of molecular structures by EM,

Was this article helpful?

0 0
Aspergers Answers Revealed

Aspergers Answers Revealed

Learn How to Help, Understand amp Cope with your Aspergers Child from a UK Chartered Educational Psychologist. Before beginning any practice relating to Aspergers it is highly recommended that you first obtain the consent and advice of a qualified health,education or social care professional.

Get My Free Ebook


Post a comment