title: Contactin-associated protein (Caspr) and contactin form a complex that is targeted to the paranodal junctions during myelination.
abstract: Specialized paranodal junctions form between the axon and the closely apposed paranodal loops of myelinating glia. They are interposed between sodium channels at the nodes of Ranvier and potassium channels in the juxtaparanodal regions; their precise function and molecular composition have been elusive. We previously reported that Caspr (contactin-associated protein) is a major axonal constituent of these junctions (Einheber et al., 1997). We now report that contactin colocalizes and forms a cis complex with Caspr in the paranodes and juxtamesaxon. These proteins coextract and coprecipitate from neurons, myelinating cultures, and myelin preparations enriched in junctional markers; they fractionate on sucrose gradients as a high-molecular-weight complex, suggesting that other proteins may also be associated with this complex. Neurons express two contactin isoforms that differ in their extent of glycosylation: a lower-molecular-weight phosphatidylinositol phospholipase C (PI-PLC)-resistant form is associated specifically with Caspr in the paranodes, whereas a higher-molecular-weight form of contactin, not associated with Caspr, is present in central nodes of Ranvier. These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr. Treatment of myelinating cocultures of Schwann cells and neurons with RPTPbeta-Fc, a soluble construct containing the carbonic anhydrase domain of the receptor protein tyrosine phosphatase beta (RPTPbeta), a potential glial receptor for contactin, blocks the localization of the Caspr/contactin complex to the paranodes. These results strongly suggest that a preformed complex of Caspr and contactin is targeted to the paranodal junctions via extracellular interactions with myelinating glia.
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Rios
authors.forename: C V
authors.initials: CV
authors.lastname: Melendez-Vasquez
authors.forename: S
authors.initials: S
authors.lastname: Einheber
authors.forename: M
authors.initials: M
authors.lastname: Lustig
authors.forename: M
authors.initials: M
authors.lastname: Grumet
authors.forename: J
authors.initials: J
authors.lastname: Hemperly
authors.forename: E
authors.initials: E
authors.lastname: Peles
authors.forename: J L
authors.initials: JL
authors.lastname: Salzer
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D018920:Coculture Techniques; D058966:Contactins; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007365:Intercellular Junctions / Q000378:metabolism*; D008970:Molecular Weight; D009186:Myelin Sheath / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D017434:Protein Structure, Tertiary / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D011901:Ranvier's Nodes / Q000378:metabolism*; D051381:Rats; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: C491323:CNTNAP1 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C105177:Cntnap1 protein, rat; D058966:Contactins; D007141:Immunoglobulin Fc Fragments; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase