betaIV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG.
High densities of ion channels at axon initial segments (AISs) and nodes of Ranvier are required for initiation, propagation, and modulation of action potentials in axons. The organization of these membrane domains depends on a specialized cytoskeleton consisting of two submembranous cytoskeletal and scaffolding proteins, ankyrinG (ankG) and betaIV spectrin. However, it is not known which of these proteins is the principal organizer, or if the mechanisms governing formation of the cytoskeleton at the AIS also apply to nodes. We identify a distinct protein domain in betaIV spectrin required for its localization to the AIS, and show that this domain mediates betaIV spectrin's interaction with ankG. Dominant-negative ankG disrupts betaIV spectrin localization, but does not alter endogenous ankG or Na(+) channel clustering at the AIS. Finally, using adenovirus for transgene delivery into myelinated neurons, we demonstrate that betaIV spectrin recruitment to nodes of Ranvier also depends on binding to ankG.
Yang
Yang
Y
Department of Neuroscience, University of Connecticut Health Center, University of Connecticut, Farmington, CT 06032, USA.
Ogawa
Yasuhiro
Y
Hedstrom
Kristian L
KL
Rasband
Matthew N
MN
D000818:Animals; D000831:Animals, Newborn; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D001370:Axonal Transport / Q000502:physiology; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000378:metabolism; D013049:Spectrin / Q000737:chemistry / Q000378:metabolism*
C094681:Ank3 protein, mouse; D017487:Ankyrins; D015222:Sodium Channels; C504042:betaIV spectrin, mouse; D013049:Spectrin