title: Assembly and maintenance of nodes of ranvier rely on distinct sources of proteins and targeting mechanisms.
abstract: We have investigated the source(s) and targeting of components to PNS nodes of Ranvier. We show adhesion molecules are freely diffusible within the axon membrane and accumulate at forming nodes from local sources, whereas ion channels and cytoskeletal components are largely immobile and require transport to the node. We further characterize targeting of NF186, an adhesion molecule that pioneers node formation. NF186 redistributes to nascent nodes from a mobile, surface pool. Its initial accumulation and clearance from the internode require extracellular interactions, whereas targeting to mature nodes, i.e., those flanked by paranodal junctions, requires intracellular interactions. After incorporation into the node, NF186 is immobile, stable, and promotes node integrity. Thus, nodes assemble from two sources: adhesion molecules, which initiate assembly, accumulate by diffusion trapping via interactions with Schwann cells, whereas ion channels and cytoskeletal components accumulate via subsequent transport. In mature nodes, components turnover slowly and are replenished via transport.
authors.affiliation: Smilow Neuroscience Program, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yoko
authors.initials: Y
authors.lastname: Bekku
authors.forename: Yulia
authors.initials: Y
authors.lastname: Dzhashiashvili
authors.forename: Stephen
authors.initials: S
authors.lastname: Armenti
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Meng
authors.forename: Yo
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Milbrandt
authors.forename: James L
authors.initials: JL
authors.lastname: Salzer
mesh_terms: D000818:Animals; D019921:Biotinylation; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008954:Models, Biological; D004676:Myelin Basic Protein / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011901:Ranvier's Nodes / Q000502:physiology*; D051381:Rats; D012583:Schwann Cells / Q000502:physiology; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C504593:Nfasc protein, mouse; C485184:enhanced green fluorescent protein; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins