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 βIV 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.
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4 June 2007
Article|
June 04 2007
Nodes of Ranvier and axon initial segments are ankyrin G–dependent domains that assemble by distinct mechanisms
Yulia Dzhashiashvili,
Yulia Dzhashiashvili
1Department of Cell Biology,
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
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Yanqing Zhang,
Yanqing Zhang
1Department of Cell Biology,
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
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Jolanta Galinska,
Jolanta Galinska
1Department of Cell Biology,
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
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Isabel Lam,
Isabel Lam
1Department of Cell Biology,
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
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Martin Grumet,
Martin Grumet
4W.M. Keck Center for Collaborative Neuroscience and
5Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854
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James L. Salzer
James L. Salzer
1Department of Cell Biology,
2Department of Neurology, and
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
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Yulia Dzhashiashvili
1Department of Cell Biology,
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
Yanqing Zhang
1Department of Cell Biology,
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
Jolanta Galinska
1Department of Cell Biology,
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
Isabel Lam
1Department of Cell Biology,
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
Martin Grumet
4W.M. Keck Center for Collaborative Neuroscience and
5Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854
James L. Salzer
1Department of Cell Biology,
2Department of Neurology, and
3Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
Correspondence to James L. Salzer: [email protected]
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.
Received:
December 04 2006
Accepted:
May 04 2007
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2007
J Cell Biol (2007) 177 (5): 857–870.
Article history
Received:
December 04 2006
Accepted:
May 04 2007
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Citation
Yulia Dzhashiashvili, Yanqing Zhang, Jolanta Galinska, Isabel Lam, Martin Grumet, James L. Salzer; Nodes of Ranvier and axon initial segments are ankyrin G–dependent domains that assemble by distinct mechanisms . J Cell Biol 4 June 2007; 177 (5): 857–870. doi: https://doi.org/10.1083/jcb.200612012
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