The Mobility of Neurofilaments in Mature Myelinated Axons of Adult Mice.

Autor:	Fenn JD; Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210.; Medical Scientist Training Program, The Ohio State University, Columbus, Ohio 43210., Li Y; Quantitative Biology Institute and Department of Physics and Astronomy, Ohio University, Athens, Ohio 45701., Julien JP; CERVO Brain Research Centre, Department of Psychiatry and Neuroscience, Laval University, Quebec, Quebec G1J 2G3, Canada., Jung P; Quantitative Biology Institute and Department of Physics and Astronomy, Ohio University, Athens, Ohio 45701., Brown A; Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210 brown.2302@osu.edu.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2023 Mar 22; Vol. 10 (3). Date of Electronic Publication: 2023 Mar 22 (Print Publication: 2023).
DOI:	10.1523/ENEURO.0029-23.2023
Abstrakt:	Studies in cultured neurons have shown that neurofilaments are cargoes of axonal transport that move rapidly but intermittently along microtubule tracks. However, the extent to which axonal neurofilaments move in vivo has been controversial. Some researchers have proposed that most axonally transported neurofilaments are deposited into a persistently stationary network and that only a small proportion of axonal neurofilaments are transported in mature axons. Here we use the fluorescence photoactivation pulse-escape technique to test this hypothesis in intact peripheral nerves of adult male hThy1-paGFP-NFM mice, which express low levels of mouse neurofilament protein M tagged with photoactivatable GFP. Neurofilaments were photoactivated in short segments of large, myelinated axons, and the mobility of these fluorescently tagged polymers was determined by analyzing the kinetics of their departure. Our results show that >80% of the fluorescence departed the window within 3 h after activation, indicating a highly mobile neurofilament population. The movement was blocked by glycolytic inhibitors, confirming that it was an active transport process. Thus, we find no evidence for a substantial stationary neurofilament population. By extrapolation of the decay kinetics, we predict that 99% of the neurofilaments would have exited the activation window after 10 h. These data support a dynamic view of the neuronal cytoskeleton in which neurofilaments cycle repeatedly between moving and pausing states throughout their journey along the axon, even in mature myelinated axons. The filaments spend a large proportion of their time pausing, but on a timescale of hours, most of them move. Competing Interests: The authors declare no competing financial interests. (Copyright © 2023 Fenn et al.)
Databáze:	MEDLINE
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