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Vol. 16, Issue 9, 4243-4255, September 2005

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Stochastic Simulation of Neurofilament Transport in Axons: The "Stop-and-Go" Hypothesis

Anthony Brown ^*, Lei Wang , and Peter Jung 

^* Center for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210; Developmental Neurobiology Program, The Burnham Institute, La Jolla, CA 92037; and Department of Physics and Astronomy, Ohio University, Athens, OH 45701

Submitted February 19, 2005; Revised June 22, 2005; Accepted June 23, 2005
Monitoring Editor: Erika Holzbaur

According to the "stop-and-go" hypothesis of slow axonal transport, cytoskeletal and cytosolic proteins are transported along axons at fast rates but the average velocity is slow because the movements are infrequent and bidirectional. To test whether this hypothesis can explain the kinetics of slow axonal transport in vivo, we have developed a stochastic model of neurofilament transport in axons. We propose that neurofilaments move in both anterograde and retrograde directions along cytoskeletal tracks, alternating between short bouts of rapid movement and short "on-track" pauses, and that they can also temporarily disengage from these tracks, resulting in more prolonged "off-track" pauses. We derive the kinetic parameters of the model from a detailed analysis of the moving and pausing behavior of single neurofilaments in axons of cultured neurons. We show that the model can match the shape, velocity, and spreading of the neurofilament transport waves obtained by radioisotopic pulse labeling in vivo. The model predicts that axonal neurofilaments spend 8% of their time on track and 97% of their time pausing during their journey along the axon.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Anthony Brown (brown.2302{at}osu.edu).

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