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PMID: 17548513 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Nodes of Ranvier and axon initial segments are ankyrin G-dependent domains that assemble by distinct mechanisms.

The Journal of cell biology ·Vol. 177 ·No. 5 ·2007-06-04 ·Pages 857-70

Dzhashiashvili Y, Zhang Y, Galinska J, Lam I, Grumet M, Salzer JL

Abstract

Axon initial segments (AISs) and nodes of Ranvier are sites of action potential generation and propagation, respectively. Both domains are enriched in sodium channels complexed with adhesion molecules (neurofascin [NF] 186 and NrCAM) and cytoskeletal proteins (ankyrin G and betaIV spectrin). We show that the AIS and peripheral nervous system (PNS) nodes both require ankyrin G but assemble by distinct mechanisms. The AIS is intrinsically specified; it forms independent of NF186, which is targeted to this site via intracellular interactions that require ankyrin G. In contrast, NF186 is targeted to the node, and independently cleared from the internode, by interactions of its ectodomain with myelinating Schwann cells. NF186 is critical for and initiates PNS node assembly by recruiting ankyrin G, which is required for the localization of sodium channels and the entire nodal complex. Thus, initial segments assemble from the inside out driven by the intrinsic accumulation of ankyrin G, whereas PNS nodes assemble from the outside in, specified by Schwann cells, which direct the NF186-dependent recruitment of ankyrin G.

MeSH Terms
Animals Ankyrins/antagonists & inhibitors,physiology Axons/metabolism,physiology,ultrastructure Cell Adhesion Molecules/chemistry,metabolism Cells, Cultured Nerve Growth Factors/chemistry,metabolism Protein Structure, Tertiary Ranvier's Nodes/metabolism,physiology,ultrastructure Rats Sodium Channels/metabolism
Chemicals
Ank3 protein, rat Ankyrins Cell Adhesion Molecules Nerve Growth Factors Nfasc protein, rat NrCAM protein, rat Sodium Channels
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Dzhashiashvili Yulia
Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
Zhang Yanqing
Galinska Jolanta
Lam Isabel
Grumet Martin
Salzer James L
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200612012
Published
2007-06-04
Pages
857-70
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064285
Subset
IM
Grants
NINDS NIH HHS · R01 NS043474 · United States
NINDS NIH HHS · NS43474 · United States
External Links
PubMed source DOI: 10.1083/jcb.200612012 PMC Full Text View journal details
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