Anterograde axonal transport

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. 

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FIGURE 2. A schematic representation showing the two classes of raphe-cortical axon terminals that were identified by anterograde axon transport... 

Subsequent anatomical techniques (e.g. immunohisto-chemistry of 5-HT or tryptophan hydroxylase, an enzyme unique to the synthesis of 5-HT retrograde and anterograde axonal transport studies) have allowed a more complete and accurate characterization of the serotonergic innervation of forebrain areas. 

Koo, E. H., Sisodia, S. S., Archer, D. R. et al. Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc. Natl Acad. Sci. USA 87 1561-1565, 1990. 

The axonal transport of APP in neurons is mediated by the direct binding of APP to the kinesin light chain subunit of kinesin I. An axonal membrane compartment contains APP, P-secretase, and PSl, and the fast anterograde axonal transport of this compartment is mediated by APP and kinesin I. APP proteolysis in this... 

Kawamura K, Hashikawa T (1979) Olivocerebellar projections in the cat studied by means of anterograde axonal transport of labeled amino acids as tracers. Neuroscience, 4, 1615-1633. 

Ferguson I, Schweitzer J, Johnson EMJ. Basic fibroblast growth factor receptor-mediated internalization, metabolism, and anterograde axonal transport in retinal ganglion cells. J Neurosci 1990 10 2176-2189. 

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. 

FIGURE 28-3 Two-dimensional fluorographs showing the 35S methionine-labeled polypeptides in the three major anterograde rate components of axonal transport SCa, slow component a SCb, slow component b FC, fast component. Note that rate component not only has a characteristic rate but a characteristic polypeptide composition. The discovery that each rate component has a different polypeptide composition led to the structural hypothesis. (With permission from Tytell, M. etal. SciencellA 179-181, 1981 [6] illustration provided by Dr. Michael Tytell.)... 

FIGURE 28-5 Schematic illustration of the movement of cytoskeletal elements in slow axonal transport. Slow axonal transport represents the movement of cytoplasmic constituents including cytoskeletal elements and soluble enzymes of intermediary metabolism at rates of 0.2-2 mm/day which are at least two orders of magnitude slower than those observed in fast axonal transport. As proposed in the structural hypothesis and supported by experimental evidence, cytoskeletal components are believed to be transported down the axon in their polymeric forms, not as individual subunit polypeptides. Cytoskeletal polypeptides are translated on cytoplasmic polysomes and then are assembled into polymers prior to transport down the axon in the anterograde direction. In contrast to fast axonal transport, no constituents of slow transport appear to be transported in the retrograde direction. Although the polypeptide composition of slow axonal transport has been extensively characterized, the motor molecule(s) responsible for the movement of these cytoplasmic constituents has not yet been identified. 

Sahenk, Z. and Lasek, R. J. Inhibition of proteolysis blocks anterograde-retrograde conversion of axonally transported vesicles. Brain Res. 460 199-203,1988. 

Axons transport materials from the cell body to the synaptic terminals (anterograde transport) and in the opposite direction (retrograde transport). Anterograde transport may occur slowly (a few millimeters/ day only) or fast (up to 400 mm/day), whereas retrograde transport is always fast. Diffusion in the perpendicular direction (not along axons) is much more limited as the membranes and the myelin sheath form obstacles. Therefore, diffusion is not isotropic (same in all directions) in the WM. This phenomenon is known as diffusion anisotropy . In contrast, diffusion is rel-... 

Gerfen CR, Sawchenko PE (1984) An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L). Brain Res 290 219-238. 

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