Neurofascin assembles a specialized extracellular matrix at the axon initial segment.

Authors: Hedstrom, Kristian L  Xu, Xiaorong  Ogawa, Yasuhiro  Frischknecht, Renato  Seidenbecher, Constanze I  Shrager, Peter  Rasband, Matthew N 
Citation: Hedstrom KL, etal., J Cell Biol. 2007 Aug 27;178(5):875-86. doi: 10.1083/jcb.200705119. Epub 2007 Aug 20.
Pubmed: (View Article at PubMed) PMID:17709431
DOI: Full-text: DOI:10.1083/jcb.200705119

Action potential initiation and propagation requires clustered Na(+) (voltage-gated Na(+) [Nav]) channels at axon initial segments (AIS) and nodes of Ranvier. In addition to ion channels, these domains are characterized by cell adhesion molecules (CAMs; neurofascin-186 [NF-186] and neuron glia-related CAM [NrCAM]), cytoskeletal proteins (ankyrinG and betaIV spectrin), and the extracellular chondroitin-sulfate proteoglycan brevican. Schwann cells initiate peripheral nervous system node formation by clustering NF-186, which then recruits ankyrinG and Nav channels. However, AIS assembly of this protein complex does not require glial contact. To determine the AIS assembly mechanism, we silenced expression of AIS proteins by RNA interference. AnkyrinG knockdown prevented AIS localization of all other AIS proteins. Loss of NF-186, NrCAM, Nav channels, or betaIV spectrin did not affect other neuronal AIS proteins. However, loss of NF-186 blocked assembly of the brevican-based AIS extracellular matrix, and NF-186 overexpression caused somatodendritic brevican clustering. Thus, NF-186 assembles and links the specialized brevican-containing AIS extracellular matrix to the intracellular cytoskeleton.


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CRRD Object Information
CRRD ID: 14392774
Created: 2019-02-27
Species: All species
Last Modified: 2019-02-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.