Fast axonal transport

MTs extend from the centrosome throughout the cytoplasm to the plasma membrane, where they are stabilized by caps. Sliding along the MTs, kinesin and dynein motors transport their cargoes between the center and the periphery of the cell. MTs present in the axons of neur ons are extended not only by addition of heterodimers to the plus ends but also by use of short MTs that initiate in the centrosome. Their axonal transport is mediated by dynein motors that are passively moved along actin filaments. Once formed in the axon, MTs serve as tracks for the fast axonal transport, i.e. the movement of membranous organelles and membrane proteins to the nerve ending. 

Features of fast axonal transport demonstrated by biochemical and pharmacological approaches are apparent from video images 488... 

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. 

Drug studies demonstrated a requirement that most proteins destined for fast axonal transport traverse the Golgi stacks, where membrane proteins are post-transla-tionally modified, sorted and packaged [9] (Fig. 28-7). This suggests that proteins in fast axonal transport must either pass through the Golgi complex or associate with... 

Video microscopy allows study of molecular mechanisms through direct observation of organelle movements while precise control of experimental conditions is maintained. Fast axonal transport continues unabated in isolated axoplasm from giant axons of the squid Loligo pealeii for hours [14]. Video microscopy applied to isolated axoplasm permits a more rigorous dissection of the molecular mechanisms for fast axonal transport... 

Dephosphorylated synapsin inhibits axonal transport of MBOs in isolated axoplasm, while phosphorylated synapsin at similar concentrations has no effect [21]. When a synaptic vesicle passes through a region rich in dephosphorylated synapsin, it may be cross-linked to the available MF matrix by synapsin. Such cross-linked vesicles would be removed from fast axonal transport and are effectively targeted to a synapsin- and MF-rich domain, the presynaptic terminal. 

In neurons and non-neuronal cells, kinesin is associated with a variety of MBOs, ranging from synaptic vesicles to mitochondria to lysosomes. In addition to its role in fast axonal transport and related phenomena in non-neuronal cells, kinesin appears to be involved in constitutive cycling of membranes between the Golgi and endoplasmic reticulum. However, kinesin is not associated with all cellular membranes. For example, the nucleus, membranes of the Golgi complex and the plasma membrane all appear to lack kinesin. Kinesin interactions with membranes are thought to involve the light chains and carboxyl termini of heavy chains. However, neither this selectivity nor the molecular basis for binding of kinesin and other motors to membranes is well understood. 

Brady, S. T., Lasek, R. J. and Allen, R. D. Fast axonal transport in extruded axoplasm from squid giant axon. Cell Mot. 3 (Video Supplement), 1983. 

Hammerschlag, R., Stone, G. C., Bolen, F. A., Lindsey, J. D. and Ellisman, M. H. Evidence that all newly synthesized proteins destined for fast axonal transport pass through the Golgi apparatus. J. Cell Biol. 93 568-575,1982. 

Schroer, T. A., Brady, S. T. and Kelly, R. Fast axonal transport of foreign vesicles in squid axoplasm. /. Cell Biol. 101 568-572, 1985. 

Lasek, R. J. and Brady, S. T. Adenylyl imidodiphosphate (AMPPNP), a nonhydrolyzable analogue of ATP, produces a stable intermediate in the motility cycle of fast axonal transport. Biol. Bull. 167 503,1984. 

Brady, S. T. A novel brain ATPase with properties expected for the fast axonal transport motor. Nature 317 73-75, 1985. 

Elluru, R., Bloom, G. S. and Brady, S. T. Fast axonal transport of kinesin in the rat visual system functionality of the kinesin heavy chain isoforms. Mol. Biol. Cell 6 21-40,1995. 

Griffin, I. W., Fahnestock, K. E., Price, D. L. and Hoffman, P. N. Microtubule-neurofilament segregation produced by P,P - iminodipropionitrile evidence for the association of fast axonal transport with microtubules. /. Neurosci. 3 557-566,1983. 

The cytosol is the fluid compartment of the cell and contains the enzymes responsible for cellular metabolism together with free ribosomes concerned with local protein synthesis. In addition to these structures which are common to all cell types, the neuron also contains specific organelles which are unique to the nervous system. For example, the neuronal skeleton is responsible for monitoring the shape of the neuron. This is composed of several fibrous proteins that strengthen the axonal process and provide a structure for the location of specific membrane proteins. The axonal cytoskeleton has been divided into the internal cytoskeleton, which consists of microtubules linked to filaments along the length of the axon, which provides a track for the movement of vesicular material by fast axonal transport, and the cortical cytoskeleton. 

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... 

In fast axonal transport, dynein motors serve to bring vesicles from near the end of the axon (the plus end of the microtubules) toward the cell body (the minus end of the microtubules). The distance traveled can be as much as a meter. Since dynein is a minus-end directed motor, how does it get out to the plus ends of the microtubules in the first place ... 

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