Axonal transport elements

The structural hypothesis, which was formulated in response to observations that axonal transport rate components move as discrete waves, each with a characteristic rate and a distinctive composition, can explain the coherent transport of functionally related proteins and is consistent with the relatively small numbers of motor molecules in neurons. The only assumption is that the number of elements that can interact with transport motor complexes is limited, and this requires appropriate packaging of the transported material. Different rate components result from packaging of transported material into different, cytologically identifiable, structures. In fact, the faster rates reflect the transport of proteins preassembled as membranous organelles, including vesicles and... 

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. 

Finally, this section has focused almost entirely on axonal transport, but dendritic transport also occurs [25]. Since dendrites usually include postsynaptic regions while most axons terminate in presynaptic elements, the dendritic and axonal transport each receive a number of unique proteins. An added level of complexity for intraneuronal transport phenomena is the intriguing observation that mRNA is routed into dendrites where it is implicated in local protein synthesis at postsynaptic sites, but ribosomal components and mRNA are largely excluded from axonal domains [26]. Regulation of protein synthesis in dendritic compartments is an important mechanism is synaptic plasticity [27,28]. The importance of dendritic mRNA transport and local protein synthesis is underscored by the demonstration that the mutation associated with Fragile X syndrome affects a protein important for transport and localization of mRNA in dendrites [27, 29], Similar processes of mRNA transport have been described in glial cells [30]. 

Cytoplasmic and cytoskeletal elements move coherently at slow transport rates. Two major rate components have been described for slow axonal transport, representing movement of cytoplasmic constituents including cytoskeletal elements and soluble enzymes of intermediary metabolism [3]. Cytoplasmic and cytoskeletal elements in axonal transport move with rates at least two orders of magnitude slower than fast transport. 

Properties of slow transport suggest molecular mechanisms. Information about mechanisms of slow axonal transport is relatively limited. They are energy-dependent and require an intact axonal cytoskeleton. Indirect evidence suggests that MTs play a critical role, because transport of NFs can be pharmacologically uncoupled from MT transport without eliminating slow transport [33]. In contrast, all agents that disrupt MTs appear to block slow transport of all components. While this does not rule out a role for the MF cytoskeleton in slow transport movements, MTs appear to provide motive force for other elements of the cytoskeleton. 

Lasek, R. J. and Brady, S. T. The Structural Hypothesis of axonal transport Two classes of moving elements. In D. G. Weiss (ed.), Axoplasmic Transport. Berlin Springer-Verlag, 1982, pp. 397-405. 

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 NFT are an abnormal intracytoplasmatic accumulation of neurofilaments. They develop within the nerve cell soma, from where they can extend into the dendrites. The parent cell may disappear and the NFT persist as ghost tangles (Braak and Braak, 1991). Ultrastructural investigations of the NFT show that they are composed of altered neurofilament peptides that form paired helical filaments (PHF). The PHF are composed of two identical filaments twisted around each other with a periodicity of 80 nm (Perl and Pendlebury, 1987). The PHF are insoluble, covalent-bound cytoskeletal elements of high stability that, therefore, could disrupt intraneuronal axonal transport and cytoskeletal metabolism. 

Even stationary cells, which predominate in the body, may exhibit dramatic changes in their morphology—the contraction of muscle cells, the elongation of nerve axons, the formation of cell-surface protrusions, the constriction of a dividing cell in mitosis. Even more subtle than these movements are those that take place within cells—the active separation of chromosomes, the streaming of cytosol, the transport of membrane vesicles. These internal movements are essential elements in the growth and differentiation of cells, carefully controlled by the cell to take place at specified times and in particular locations. 

---