title: Neurofascin 140 is an embryonic neuronal neurofascin isoform that promotes the assembly of the node of Ranvier.
abstract: Rapid nerve conduction in myelinated nerves requires the clustering of voltage-gated sodium channels at nodes of Ranvier. The Neurofascin (Nfasc) gene has a unique role in node formation because it encodes glial and neuronal isoforms of neurofascin (Nfasc155 and Nfasc186, respectively) with key functions in assembling the nodal macromolecular complex. A third neurofascin, Nfasc140, has also been described; however, neither the cellular origin nor function of this isoform was known. Here we show that Nfasc140 is a neuronal protein strongly expressed during mouse embryonic development. Expression of Nfasc140 persists but declines during the initial stages of node formation, in contrast to Nfasc155 and Nfasc186, which increase. Nevertheless, Nfasc140, like Nfasc186, can cluster voltage-gated sodium channels (Nav) at the developing node of Ranvier and can restore electrophysiological function independently of Nfasc155 and Nfasc186. This suggests that Nfasc140 complements the function of Nfasc155 and Nfasc186 in initial stages of the assembly and stabilization of the nodal complex. Further, Nfasc140 is reexpressed in demyelinated white matter lesions of postmortem brain tissue from human subjects with multiple sclerosis. This expands the critical role of the Nfasc gene in the function of myelinated axons and reveals further redundancy in the mechanisms required for the formation of this crucial structure in the vertebrate nervous system.
authors: Centre for Neuroregeneration, The Medical School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom, and.
authors: Ao
authors: A
authors: Zhang
authors: Centre for Neuroregeneration, The Medical School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom, and.
authors: Anne
authors: A
authors: Desmazieres
authors: Centre for Neuroregeneration, The Medical School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom, and.
authors: Barbara
authors: B
authors: Zonta
authors: Centre for Neuroregeneration, The Medical School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom, and.
authors: Shona
authors: S
authors: Melrose
authors: Centre for Neuroregeneration, The Medical School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom, and.
authors: Graham
authors: G
authors: Campbell
authors: Centre for Neuroregeneration, The Medical School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom, and.
authors: Don
authors: D
authors: Mahad
authors: Centre for Neuroregeneration, The Medical School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom, and.
authors: Qiushi
authors: Q
authors: Li
authors: Centre for Neuroregeneration, The Medical School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom, and.
authors: Diane L
authors: DL
authors: Sherman
authors: Centre for Neuroinflammation and Neurodegeneration, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.
authors: Richard
authors: R
authors: Reynolds
authors: Centre for Neuroregeneration, The Medical School, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom, and Peter.Brophy@ed.ac.uk.
authors: Peter J
authors: PJ
authors: Brophy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001369:Axons / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism*; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D020033:Protein Isoforms; D061566:Voltage-Gated Sodium Channels
keywords: Nfasc140; axon initial segment; myelin; neurofascin; node of Ranvier
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