BetaIVSigma1 spectrin stabilizes the nodes of Ranvier and axon initial segments.
Saltatory electric conduction requires clustered voltage-gated sodium channels (VGSCs) at axon initial segments (AIS) and nodes of Ranvier (NR). A dense membrane undercoat is present at these sites, which is thought to be key for the focal accumulation of channels. Here, we prove that betaIVSigma1 spectrin, the only betaIV spectrin with an actin-binding domain, is an essential component of this coat. Specifically, betaIVSigma1 coexists with betaIVSigma6 at both AIS and NR, being the predominant spectrin at AIS. Removal of betaIVSigma1 alone causes the disappearance of the nodal coat, an increased diameter of the NR, and the presence of dilations filled with organelles. Moreover, in myelinated cochlear afferent fibers, VGSC and ankyrin G clusters appear fragmented. These ultrastructural changes can explain the motor and auditory neuropathies present in betaIVSigma1 -/- mice and point to the betaIVSigma1 spectrin isoform as a master-stabilizing factor of AIS/NR membranes.
Lacas-Gervais
Sandra
S
Medical School, University of Technology-Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Guo
Jun
J
Strenzke
Nicola
N
Scarfone
Eric
E
Kolpe
Melanie
M
Jahkel
Monika
M
De Camilli
Pietro
P
Moser
Tobias
T
Rasband
Matthew N
MN
Solimena
Michele
M
D000818:Animals; D000831:Animals, Newborn; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism; D001306:Auditory Pathways / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D003056:Cochlear Nerve / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure; D005072:Evoked Potentials, Auditory / Q000235:genetics; D005260:Female; D034381:Hearing Loss / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009420:Nervous System / Q000196:embryology* / Q000254:growth & development / Q000648:ultrastructure; D015388:Organelles / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D013049:Spectrin / Q000235:genetics / Q000502:physiology*
C490614:Ank3 protein, rat; D017487:Ankyrins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D015222:Sodium Channels; C417303:betaIV spectrin; D013049:Spectrin