Rapid axonal transport

FIGURE 17.8 (a) Rapid axonal transport along microtnbnles permits the exchange of material between the synaptic terminal and the body of the nerve cell, (b) Vesicles, mnltivesicn-lar bodies, and mitochondria are carried throngh the axon by this mechanism. 

Smith, R. S. and Snyder, R. E. Reversal of rapid axonal transport at a lesion leupeptin inhibits reversed protein transport, but does not inhibit reversed organelle transport. Brain Res. 552 215-227,1991. 

The interphase organization of microtubules serves many roles, among the most important of which is the rapid transport of organelles and materials packaged in vesicles to various parts of a cell. This process was first observed directly in the giant axons of squid and was therefore named fast axonal transport. In highly elongated... 

Slow axonal transport involves primarily components of the cytoskeleton and its protein precursors. Slow transport can be resolved into two rates, one of less than lmm/day and one of several mm/day. Components traveling at the slower rate include tubulin and its associated proteins, along with a group of three other structural proteins known as the neurofilament triplet. Components traveling at the faster rate include some tubulin, as well as actin and various soluble enzymes. It has been noted that the rate of rapid transport is constant in an animal over a range of... 

The nature of the slow transport vector and its mechanism has been the subject of intense debate for decades, but a consensus has recently been reached. Direct visualization of the movement of cytoskeletal elements within axons has demonstrated that these structures have an instantaneous transport rate that is equivalent to rapid transport and that is powered by the fast transport motors. Like mitochondria, the rapid movement of cytoskeletal elements is interrupted by long stationary periods, leading to a very slow net transport rate. Thus there is now a unified theory of all of anterograde axonal transport. 

Smith RS (1988a) Studies on the mechanism of the reversal of rapid organelle transport in myelinated axons of Xenopus laevis. Cell Motil Cytoskeleton 10 296-308. 

EXPERIMENTAL FIGURE 20-17 The rate of axonal transport in vivo can be determined by radiolabeling and gel electrophoresis. The cell bodies of neurons In the sciatic nerve are located In dorsal-root ganglia. Radioactive amino acids Injected Into these ganglia In experimental animals are Incorporated Into newly synthesized proteins, which are then transported down the axon to the synapse. Animals are sacrificed at various times after Injection and the dissected sciatic nerve Is cut Into small segments for analysis with the use of gel electrophoresis. The red, blue, and purple dots represent groups of proteins that are transported down the axon at different rates, red most rapidly, purple least rapidly. 

Kokaia Z, Andsberg G, Yan Q, Lindvall O. Rapid alterations of BDNF protein levels in the rat brain after focal ischemia evidence for increased synthesis and anterograde axonal transport. Exp Neurol 1998 154 289-301. 

As shown in Fig. 3 (Top Panel), dietary tyrosine is transported into axon terminals of DA neurons and converted in the cytoplasm to DOPA by the rate limiting enzyme TH. DOPA is then rapidly decarboxylated by DDC to DA which is taken up and stored in synaptic vesicles until release. Excess newly synthesized DA is metabolized by mitochondrial monoamine oxidase (MAO) to DOPAC which rapidly diffuses out of neurons and is taken up and converted to homovanillic acid (HVA) by catechol-O-methyltransferase (COMT)-containing glial cells in the neuropil (Hansson and Sellstrom, 1983 Kimelberg, 1986). Upon arrival of an action potential at the axon terminal, vesicular DA is released into the synapse via calcium-dependent exocytosis where it is free to interact with stimulatory Di and/or inhibitory D2 DA receptors on postsynaptic target cells and inhibitory D2 autoreceptors on presynaptic terminals. A major portion of DA is removed from the synapse by high affinity DA transporters located on presynaptic terminals, and recaptured DA is either metabolized to DOPAC by mitochondrial MAO or stored in synaptic vesicles for subsequent re-release. A small portion of DA can also be taken up from the synapse by glia and metabolized to 3-methoxytyramine (3MT) and HVA. 

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