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The Journal of Neuroscience, November 15, 2000, 20(22):8354-8364
Contactin-Associated Protein (Caspr) and Contactin Form a Complex
That Is Targeted to the Paranodal Junctions during Myelination
Jose C.
Rios1,
Carmen
V.
Melendez-Vasquez1,
Steven
Einheber1,
Marc
Lustig2,
Martin
Grumet2,
John
Hemperly5,
Elior
Peles6, and
James L.
Salzer1, 3, 4
Departments of 1 Cell Biology,
2 Pharmacology, 3 Neurology, and the
4 Kaplan Cancer Center, New York University School of
Medicine, New York, New York 10016, 5 BD Technologies,
Research Triangle Park, North Carolina 27709, and
6 Department of Molecular Cell Biology, The Weizmann
Institute of Science, Rehovot 76100, Israel
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 RPTP -Fc, a soluble construct containing the
carbonic anhydrase domain of the receptor protein tyrosine phosphatase
(RPTP), 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.
Key words:
myelin; axons; Caspr; contactin; nodes of Ranvier; paranode
Copyright © 2000 Society for Neuroscience 0270-6474/00/20228354-11$05.00/0
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