Internode length is reduced during myelination and remyelination by neurofilament medium phosphorylation in motor axons.

Autor: Villalón E; Department of Biological Sciences, University of Missouri, Columbia, MO 65211, United States; C.S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, United States., Barry DM; Department of Anesthesiology, Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, United States., Byers N; Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States., Frizzi K; Department of Pathology, University of California San Diego, La Jolla, CA 92093, United States., Jones MR; Department of Biological Sciences, University of Missouri, Columbia, MO 65211, United States; C.S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, United States., Landayan DS; Department of Quantitative and Systems Biology, University of California Merced, Merced, CA 95343, United States., Dale JM; Department of Biological Sciences, University of Missouri, Columbia, MO 65211, United States; C.S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, United States., Downer NL; Department of Biological Science, Moberly Area Community College, Moberly, MO 65270, United States., Calcutt NA; Department of Pathology, University of California San Diego, La Jolla, CA 92093, United States., Garcia ML; Department of Biological Sciences, University of Missouri, Columbia, MO 65211, United States; C.S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, United States. Electronic address: GarciaML@missouri.edu.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2018 Aug; Vol. 306, pp. 158-168. Date of Electronic Publication: 2018 May 14.
DOI: 10.1016/j.expneurol.2018.05.009
Abstrakt: The distance between nodes of Ranvier, referred to as internode length, positively correlates with axon diameter, and is optimized during development to ensure maximal neuronal conduction velocity. Following myelin loss, internode length is reestablished through remyelination. However, remyelination results in short internode lengths and reduced conduction rates. We analyzed the potential role of neurofilament phosphorylation in regulating internode length during remyelination and myelination. Following ethidium bromide induced demyelination, levels of neurofilament medium (NF-M) and heavy (NF-H) phosphorylation were unaffected. Preventing NF-M lysine-serine-proline (KSP) repeat phosphorylation increased internode length by 30% after remyelination. To further analyze the role of NF-M phosphorylation in regulating internode length, gene replacement was used to produce mice in which all KSP serine residues were replaced with glutamate to mimic constitutive phosphorylation. Mimicking constitutive KSP phosphorylation reduced internode length by 16% during myelination and motor nerve conduction velocity by ~27% without altering sensory nerve structure or function. Our results suggest that NF-M KSP phosphorylation is part of a cooperative mechanism between axons and Schwann cells that together determine internode length, and suggest motor and sensory axons utilize different mechanisms to establish internode length.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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