Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin.
Myelinated fibers are organized into distinct domains that are necessary for saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where glial cells closely appose and form specialized septate-like junctions with axons. These junctions contain a Drosophila Neurexin IV-related protein, Caspr/Paranodin (NCP1). Mice that lack NCP1 exhibit tremor, ataxia, and significant motor paresis. In the absence of NCP1, normal paranodal junctions fail to form, and the organization of the paranodal loops is disrupted. Contactin is undetectable in the paranodes, and K(+) channels are displaced from the juxtaparanodal into the paranodal domains. Loss of NCP1 also results in a severe decrease in peripheral nerve conduction velocity. These results show a critical role for NCP1 in the delineation of specific axonal domains and the axon-glia interactions required for normal saltatory conduction.
Bhat
M A
MA
Cardiovascular Research Institute, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. bhatm01@doc.mssm.edu
Rios
J C
JC
Lu
Y
Y
Garcia-Fresco
G P
GP
Ching
W
W
St Martin
M
M
Li
J
J
Einheber
S
S
Chesler
M
M
Rosenbluth
J
J
Salzer
J L
JL
Bellen
H J
HJ
D000375:Aging; D000818:Animals; D001369:Axons / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal; D003001:Cloning, Molecular; D004330:Drosophila; D029721:Drosophila Proteins; D005260:Female; D015698:Genomic Library; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000502:physiology* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D015183:Restriction Mapping; D012584:Sciatic Nerve / Q000502:physiology*
C491323:CNTNAP1 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C491321:Nrx protein, Drosophila; D015221:Potassium Channels; D011956:Receptors, Cell Surface