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Published online
doi:10.1083/jcb.200612012
The Journal of Cell Biology, Vol. 177, No. 5, 857-870
The Rockefeller University Press, 0021-9525 $30.00
© Dzhashiashvili et al.
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Article

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



Yulia Dzhashiashvili1,3, Yanqing Zhang1,3, Jolanta Galinska1,3, Isabel Lam1,3, Martin Grumet4,5, and James L. Salzer1,2,3

1 Department of Cell Biology, 2 Department of Neurology, and 3 Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
4 W.M. Keck Center for Collaborative Neuroscience and 5 Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854

Correspondence to James L. Salzer: Salzer{at}Saturn.med.nyu.edu

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 ßIV 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.

Abbreviations used in this paper: ABD, ankyrin binding domain; AIS, axon initial segment; CAM, cell adhesion molecule; DRG, dorsal root ganglion; FNIII, fibronectin type III; Hc, hippocampal; ICAM1, intercellular adhesion molecule 1; MAP2, microtubule-associated protein 2; NF, neurofascin; PNS, peripheral nervous system; PS, proximal segment; shRNA, short hairpin RNA; wt, wild-type.


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