title: A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier.
abstract: The scaffolding protein ankyrin-G is required for Na(+) channel clustering at axon initial segments. It is also considered essential for Na(+) channel clustering at nodes of Ranvier to facilitate fast and efficient action potential propagation. However, notwithstanding these widely accepted roles, we show here that ankyrin-G is dispensable for nodal Na(+) channel clustering in vivo. Unexpectedly, in the absence of ankyrin-G, erythrocyte ankyrin (ankyrin-R) and its binding partner βI spectrin substitute for and rescue nodal Na(+) channel clustering. In addition, channel clustering is also rescued after loss of nodal βIV spectrin by βI spectrin and ankyrin-R. In mice lacking both ankyrin-G and ankyrin-R, Na(+) channels fail to cluster at nodes. Thus, ankyrin R-βI spectrin protein complexes function as secondary reserve Na(+) channel clustering machinery, and two independent ankyrin-spectrin protein complexes exist in myelinated axons to cluster Na(+) channels at nodes of Ranvier.
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Tammy Szu-Yu
authors.initials: TS
authors.lastname: Ho
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Zollinger
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Kae-Jiun
authors.initials: KJ
authors.lastname: Chang
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Mingxuan
authors.initials: M
authors.lastname: Xu
authors.affiliation: 1] Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA. [2] Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Cooper
authors.affiliation: Department of Pathology, Yale University, New Haven, Connecticut, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Stankewich
authors.affiliation: Department of Cell Biology, Duke University, Durham, North Carolina, USA.
authors.forename: Vann
authors.initials: V
authors.lastname: Bennett
authors.affiliation: 1] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA. [2] Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Rasband
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011901:Ranvier's Nodes / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000032:analysis* / Q000378:metabolism; D013049:Spectrin / Q000032:analysis* / Q000378:metabolism
chemical_list: D017487:Ankyrins; D015222:Sodium Channels; D013049:Spectrin