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

Yulia Dzhashiashvili, Yanqing Zhang, Jolanta Galinska, Isabel Lam, Martin Grumet, James L. Salzer

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

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 ?IV 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.

Original languageEnglish (US)
Pages (from-to)857-870
Number of pages14
JournalJournal of Cell Biology
Volume177
Issue number5
DOIs
StatePublished - Jun 4 2007

All Science Journal Classification (ASJC) codes

  • Cell Biology

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