Neurofascin assembles a specialized extracellular matrix at the axon initial segment.
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.
Hedstrom
Kristian L
KL
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06032, USA.
Xu
Xiaorong
X
Ogawa
Yasuhiro
Y
Frischknecht
Renato
R
Seidenbecher
Constanze I
CI
Shrager
Peter
P
Rasband
Matthew N
MN
D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D058581:Brevican; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D037181:Lectins, C-Type / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011901:Ranvier's Nodes / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013049:Spectrin / Q000235:genetics / Q000378:metabolism
C490614:Ank3 protein, rat; D017487:Ankyrins; C546939:Bcan protein, rat; D058581:Brevican; D015815:Cell Adhesion Molecules; D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C504594:Nfasc protein, rat; C504754:NrCAM protein, rat; D011993:Recombinant Fusion Proteins; D015222:Sodium Channels; D013049:Spectrin; D012313:RNA
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