Caspr regulates the processing of contactin and inhibits its binding to neurofascin.
Three cell adhesion molecules are present at the axoglial junctions that form between the axon and myelinating glia on either side of nodes of Ranvier. These include an axonal complex of contacin-associated protein (Caspr) and contactin, which was proposed to bind NF155, an isoform of neurofascin located on the glial paranodal loops. Here, we show that NF155 binds directly to contactin and that surprisingly, coexpression of Caspr inhibits this interaction. This inhibition reflects the association of Caspr with contactin during biosynthesis and the resulting expression of a low molecular weight (LMw), endoglycosidase H-sensitive isoform of contactin at the cell membrane, which remains associated with Caspr but is unable to bind NF155. Accordingly, deletion of Caspr in mice by gene targeting results in a shift from the LMw- to a HMw-contactin glycoform. These results demonstrate that Caspr regulates the intracellular processing and transport of contactin to the cell surface, thereby affecting its ability to interact with other cell adhesion molecules.
Gollan
Leora
L
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100 Israel.
Salomon
Daniela
D
Salzer
James L
JL
Peles
Elior
E
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D058966:Contactins; D018390:Gene Targeting; D006031:Glycosylation; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008970:Molecular Weight; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D058966:Contactins; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D020033:Protein Isoforms