TY - JOUR
T1 - Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon
AU - Boiko, Tatiana
AU - Rasband, Matthew N.
AU - Levinson, S. Rock
AU - Caldwell, John H.
AU - Mandel, Gail
AU - Trimmer, James S.
AU - Matthews, Gary
N1 - Funding Information:
We thank Joan Speh for help with confocal microscopy and for technical advice, Dr. Steve Yazulla for advice on immunocytochemistry, Dr. Melita Schachner for anti-MAG monoclonal antibody, and Dr. Elena Battaglioli for helpful discussions. Excellent technical assistance in antibody production and screening was provided by Diane Henry, Lynn Buchwalder, and Dan Sherbenou. Supported by NIH grants EY03821 (G. Matthews), NS10906 (M. N. R.), NS22518 (G. Mandel), NS26505 (J. H. C.), NS34375 (S. R. L.), and NS34383 (J. S. T.) and by a grant from the Spinal Cord Research Foundation (M. N. R.). G. Mandel is an Investigator of the Howard Hughes Medical Institute.
PY - 2001/4
Y1 - 2001/4
N2 - Voltage-dependent sodium channels are uniformly distributed along unmyelinated axons, but are highly concentrated at nodes of Ranvier in myelinated axons. Here, we show that this pattern is associated with differential localization of distinct sodium channel α subunits to the unmyelinated and myelinated zones of the same retinal ganglion cell axons. In adult axons, Nav1.2 is localized to the unmyelinated zone, whereas Nav1.6 is specifically targeted to nodes. During development, Nav1.2 is expressed first and becomes clustered at immature nodes of Ranvier, but as myelination proceeds, Nav1.6 replaces Nav1.2 at nodes. In Shiverer mice, which lack compact myelin, Nav1.2 is found throughout adult axons, whereas little Nav1.6 is detected. Together, these data show that sodium channel isoforms are differentially targeted to distinct domains of the same axon in a process associated with formation of compact myelin.
AB - Voltage-dependent sodium channels are uniformly distributed along unmyelinated axons, but are highly concentrated at nodes of Ranvier in myelinated axons. Here, we show that this pattern is associated with differential localization of distinct sodium channel α subunits to the unmyelinated and myelinated zones of the same retinal ganglion cell axons. In adult axons, Nav1.2 is localized to the unmyelinated zone, whereas Nav1.6 is specifically targeted to nodes. During development, Nav1.2 is expressed first and becomes clustered at immature nodes of Ranvier, but as myelination proceeds, Nav1.6 replaces Nav1.2 at nodes. In Shiverer mice, which lack compact myelin, Nav1.2 is found throughout adult axons, whereas little Nav1.6 is detected. Together, these data show that sodium channel isoforms are differentially targeted to distinct domains of the same axon in a process associated with formation of compact myelin.
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U2 - 10.1016/S0896-6273(01)00265-3
DO - 10.1016/S0896-6273(01)00265-3
M3 - Article
C2 - 11343647
AN - SCOPUS:0035034213
SN - 0896-6273
VL - 30
SP - 91
EP - 104
JO - Neuron
JF - Neuron
IS - 1
ER -