title: Local regulation of neurofilament transport by myelinating cells.
abstract: 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.
authors.affiliation: Department of Neuroscience, Ohio State University, Columbus, Ohio 43210, and Quantitative Biology Institute, Ohio University, Athens, Ohio 45701.
authors.forename: Paula C
authors.initials: PC
authors.lastname: Monsma
authors.forename: Yinyun
authors.initials: Y
authors.lastname: Li
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Fenn
authors.forename: Peter
authors.initials: P
authors.lastname: Jung
authors.forename: Anthony
authors.initials: A
authors.lastname: Brown
mesh_terms: D000465:Algorithms; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D018920:Coculture Techniques; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006019:Glycolysis / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000502:physiology; D007700:Kinetics; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D015233:Models, Statistical; D009186:Myelin Sheath / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D014162:Transfection
chemical_list: D016900:Neurofilament Proteins; D049452:Green Fluorescent Proteins
keywords: axonal transport; cell culture; cytoskeleton; fluorescence microscopy; myelination; neurofilament