Fast anterograde transport

Newly synthesized membrane and secretory proteins destined for the axon travel by fast anterograde transport 488... 

Newly synthesized membrane and secretory proteins destined for the axon travel by fast anterograde transport. However, not all membrane-bounded organelles (MBOs) are destined for the axon. As a result, the first stage of transport must be synthesis, sorting and packaging of organelles (see Ch. 9). Once assembled, the organelle must then be committed to the transport... 

Fast anterograde transport can reach rates as high as 400 mm/day. It is dependent upon microtubules that provide a track along which the vesicles move. The movement is energy dependent and is mediated by a specific motor protein, kinesin. A similar process is responsible for fast retrograde transport. A second motor protein, dynein, is needed for movement in that direction. A third type of transport process is termed slow axoplasmic transport. It ranges from 0.2 to 5 mm/day and is responsible for the transport of cytoskeletal proteins, the neurofilaments, and microtubules, as well as an assortment of cytoplasmic proteins. 

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. 

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... 

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-... 

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.)... 

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. 

The axons of neurons appear to have special transport processes for moving molecules into and out of the cell body (soma). The presence of special transport mechanisms in these cells is essential for their function, since neurons vary greatly in size, with some extending over 1 m, while protein synthesis occurs predominantly in the soma. Transport rates for different solutes occur in two categories slow (1-lOmm/day) and fast (100-400mm/day), and occur in the anterograde (away from the cell body) and retrograde (toward the cell body) directions. The speed of the slow processes is consistent with rates of diffusion, but the fast processes require additional mechanisms [9, 128]. 

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