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Vol. 16, Issue 9, 4243-4255, September 2005
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* 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).
This article has been cited by other articles:
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  A. Uchida, N. H. Alami, and A. Brown Tight Functional Coupling of Kinesin-1A and Dynein Motors in the Bidirectional Transport of Neurofilaments Mol. Biol. Cell, December 1, 2009; 20(23): 4997 - 5006. [Abstract] [Full Text] [PDF]
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 A. Yuan, T. Sasaki, M. V. Rao, A. Kumar, V. Kanumuri, D. S. Dunlop, R. K. Liem, and R. A. Nixon Neurofilaments Form a Highly Stable Stationary Cytoskeleton after Reaching a Critical Level in Axons J. Neurosci., September 9, 2009; 29(36): 11316 - 11329. [Abstract] [Full Text] [PDF]
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N. H. Alami, P. Jung, and A. Brown Myosin Va Increases the Efficiency of Neurofilament Transport by Decreasing the Duration of Long-Term Pauses J. Neurosci., May 20, 2009; 29(20): 6625 - 6634. [Abstract] [Full Text] [PDF]
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 B. Ebbing, K. Mann, A. Starosta, J. Jaud, L. Schols, R. Schule, and G. Woehlke Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity Hum. Mol. Genet., May 1, 2008; 17(9): 1245 - 1252. [Abstract] [Full Text] [PDF]
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S. Roy, M. J. Winton, M. M. Black, J. Q. Trojanowski, and V. M.-Y. Lee Rapid and Intermittent Cotransport of Slow Component-b Proteins J. Neurosci., March 21, 2007; 27(12): 3131 - 3138. [Abstract] [Full Text] [PDF]
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N. Trivedi, P. Jung, and A. Brown Neurofilaments Switch between Distinct Mobile and Stationary States during Their Transport along Axons J. Neurosci., January 17, 2007; 27(3): 507 - 516. [Abstract] [Full Text] [PDF]
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