Dyneins axonal transport

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 ... 

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. 

Dynein Motor protein mediating microtubule-based synaptic vesicle transport. May be involved in retrograde axonal transport to the cell body. 

A number of studies have implicated cytoplasmic dynein as playing a role in retrograde axonal transport [11, 39]. In vitro motility studies demonstrate that cytoplasmic dynein generates force towards the minus ends of MTs consistent with a retrograde motor. Dynein immu-noreactivities have been associated with MBOs and... 

LaMonte, B. H., Wallace, K. E., Holloway, B. A. et al. Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 34 715-727,2002. 

Dynein is probably carried out to the plus ends of axons in an inactive form, on vesicles transported along the microtubules by kinesin. Once at the axonal terminal, dynein is converted to an active form and can serve to transport vesicles back to the cell body. 

The second family of microtubule motor proteins, the dyneins, is responsible for retrograde axonal transport. 

SchnappB.J. andReeseT.S. 1989. Dynein is the motor for retrograde axonal transport of organelles. Proc. Natl Acad. Sci. USA 86 1548-1552. 

Waterman-Storer C.M., Karki S.B., KuznetsovS.A., Tabb J.S., Weiss D.G. et al. 1997. The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport. Proc. Natl Acad. Sci. USA94 12180-12185. 

The ability of dyneins to effect mechano-chemical coupling—i.e., motion coupled with a chemical reaction—is also vitally important inside eukaryotic cells, which, as already noted, contain microtubule networks as part of the cytoskele-ton. The mechanisms of intracellular, microtubule-based transport of organelles and vesicles were first elucidated in studies of axons, the long pro-... 

Figure 6. Transport of material along the nerve axon. Materials such as neurotransmitter peptides are synthesized in the cell body and sequestered in vesicles at the Golgi. Vesicles are then transported down the axon towards the synapse by kinesin motors. Other materials are transported from the synapse to the cell body by dynein motors.

Microtubules in the long axons of nerve cells function as "rails" for the "fast transport" of proteins and other materials from the cell body down the axons. In fact, microtubules appear to be present throughout the cytoplasm of virtually all eukaryotic cells (Fig. 7-32) and also in spirochetes.311 Motion in microtubular systems depends upon motor proteins such as kinesin, which moves bound materials toward what is known as the "negative" end of the microtubule,312 dyneins which move toward the positive end.310 These motor proteins are driven by the Gibbs energy of hydrolysis of ATP or GTP and in this respect, as well as in some structural details (Chapter 19), resemble the muscle protein myosin. Dynein is present in the arms of the microtubules of cilia (Fig. 1-8) whose motion results from the sliding of the microtubules driven by the action of this protein (Chapter 19). 

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