Schwannomin-interacting protein-1 isoform IQCJ-SCHIP-1 is a late component of nodes of Ranvier and axon initial segments.
Axon initial segments (AISs) and nodes of Ranvier (NRs) are essential regions for saltatory conduction of the action potential along the axon. These two domains are enriched in similar multimolecular complexes, which include voltage-gated sodium channels (Na(v)), NF186 (neurofascin 186), NrCAM (neuron glia-related cell adhesion molecule), and cytoskeleton linkers ankyrin G (AnkG) and betaIV-spectrin. Identification of novel members of these complexes is critical to better understand their formation, function, and maintenance. Here we report that IQCJ-SCHIP-1, a recently identified isoform of schwannomin-interacting protein-1 (SCHIP-1), is a novel component of both AISs and NRs in the central and peripheral nervous systems. We show that IQCJ-SCHIP-1 binds calmodulin in the absence of Ca(2+) and is highly enriched at AISs and NRs. IQCJ-SCHIP-1 accumulation at AISs and NRs is a late event, suggesting that IQCJ-SCHIP-1 is likely to play a role in mature AISs and NRs rather than during their formation. IQCJ-SCHIP-1 was not detected at AISs in the absence of AnkG and interacted in vitro with this protein. IQCJ-SCHIP-1 was also absent from central NRs and AISs of quivering mice, which have a mutation of betaIV-spectrin. We suggest that IQCJ-SCHIP-1 might participate, along with AnkG and betaIV-spectrin, in the stabilization or function of the multimolecular complexes of AISs and NRs, possibly by participating in Ca(2+)-mediated responses.
Unité Mixte de Recherche-S 839, Inserm, Université Pierre et Marie Curie, Institut du Fer à Moulin, Paris 75005, France.
Pierre-Marie
PM
Martin
Michèle
M
Carnaud
Gontzal
G
Garcia del Caño
Marie
M
Irondelle
Theano
T
Irinopoulou
Jean-Antoine
JA
Girault
Bénédicte
B
Dargent
Laurence
L
Goutebroze
D000818:Animals; D017487:Ankyrins / Q000172:deficiency; D001369:Axons / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D011901:Ranvier's Nodes / Q000378:metabolism*; D013049:Spectrin / Q000235:genetics; D014162:Transfection / Q000379:methods
D017487:Ankyrins; D002352:Carrier Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; C405019:SCHIP1 protein, human; C504042:betaIV spectrin, mouse; D013049:Spectrin; D049452:Green Fluorescent Proteins