Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion.
Nodes of Ranvier are excitable regions of axonal membranes highly enriched in voltage-gated sodium channels that propagate action potentials. The mechanism of protein clustering at nodes has been a source of controversy. In this study, developmental analysis of nodes of Ranvier in optic nerve axons reveals that early node intermediates are defined by ankyrin-G. Other node components, including beta IV spectrin, voltage-gated sodium channels, and the L1 cell adhesion molecule neurofascin, are subsequently recruited to sites of ankyrin-G clustering. The role of intact paranodes in protein clustering was examined in the dysmyelinating mouse mutant jimpy. Jimpy mice do not have intact paranodal axoglial contacts, which is indicated by a complete lack of neurexin/contactin-associated protein/paranodin clustering in paranodes. In the absence of intact paranodes, ankyrin-G was still able to cluster, although fewer ankyrin clusters were seen in jimpy optic nerves than in wild-type optic nerves. Recruitment of Na(v)1.2, Na(v)1.6, beta IV spectrin, and neurofascin to sites of ankyrin-G clustering is unimpaired in jimpy mice, indicating that node formation occurs independent of intact paranodal axoglial contacts.
Jenkins
Scott M
SM
Howard Hughes Medical Institute and Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Bennett
Vann
V
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000096:biosynthesis* / Q000737:chemistry*; D001369:Axons / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D007150:Immunohistochemistry; D051379:Mice; D008816:Mice, Jimpy; D008856:Microscopy, Fluorescence; D009186:Myelin Sheath / Q000737:chemistry; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009457:Neuroglia / Q000378:metabolism; D009900:Optic Nerve / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011901:Ranvier's Nodes / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels
C094681:Ank3 protein, mouse; C490614:Ank3 protein, rat; D017487:Ankyrins; D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; C504594:Nfasc protein, rat; D010455:Peptides; D015222:Sodium Channels