PT  - JOURNAL ARTICLE
AU  - Paula C. Monsma
AU  - Yinyun Li
AU  - J. Daniel Fenn
AU  - Peter Jung
AU  - Anthony Brown
TI  - Local Regulation of Neurofilament Transport by Myelinating Cells
AID  - 10.1523/JNEUROSCI.4502-13.2014
DP  - 2014 Feb 19
TA  - The Journal of Neuroscience
PG  - 2979--2988
VI  - 34
IP  - 8
4099  - http://www.jneurosci.org/content/34/8/2979.short
4100  - http://www.jneurosci.org/content/34/8/2979.full
SO  - J. Neurosci.2014 Feb 19; 34
AB  - Axons in the vertebrate nervous system only expand beyond ∼1 μm in diameter if they become myelinated. This expansion is due in large part to the accumulation of space-filling cytoskeletal polymers called neurofilaments, which are cargoes of axonal transport. One possible mechanism for this accumulation is a decrease in the rate of neurofilament transport. To test this hypothesis, we used a fluorescence photoactivation pulse-escape technique to compare the kinetics of neurofilament transport in contiguous myelinated and unmyelinated segments of axons in long-term myelinating cocultures established from the dorsal root ganglia of embryonic rats. The myelinated segments contained more neurofilaments and had a larger cross-sectional area than the contiguous unmyelinated segments, and this correlated with a local slowing of neurofilament transport. By computational modeling of the pulse-escape kinetics, we found that this slowing of neurofilament transport could be explained by an increase in the proportion of the time that the neurofilaments spent pausing and that this increase in pausing was sufficient to explain the observed neurofilament accumulation. Thus we propose that myelinating cells can regulate the neurofilament content and morphology of axons locally by modulating the kinetics of neurofilament transport.