Identification of a novel contactin-associated transmembrane receptor with multiple domains implicated in protein-protein interactions.
Receptor protein tyrosine phosphatase beta (RPTPbeta) expressed on the surface of glial cells binds to the glycosylphosphatidylinositol (GPI)-anchored recognition molecule contactin on neuronal cells leading to neurite outgrowth. We describe the cloning of a novel contactin-associated transmembrane receptor (p190/Caspr) containing a mosaic of domains implicated in protein-protein interactions. The extracellular domain of Caspr contains a neurophilin/coagulation factor homology domain, a region related to fibrinogen beta/gamma, epidermal growth factor-like repeats, neurexin motifs as well as unique PGY repeats found in a molluscan adhesive protein. The cytoplasmic domain of Caspr contains a proline-rich sequence capable of binding to a subclass of SH3 domains of signaling molecules. Caspr and contactin exist as a complex in rat brain and are bound to each other by means of lateral (cis) interactions in the plasma membrane. We propose that Caspr may function as a signaling component of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. The binding of RPTPbeta to the contactin-Caspr complex could provide a mechanism for cell-cell communication between glial cells and neurons during development.
Peles
E
E
Sugen, Inc., Redwood City, CA 94063, USA.
Nativ
M
M
Lustig
M
M
Grumet
M
M
Schilling
J
J
Martinez
R
R
Plowman
G D
GD
Schlessinger
J
J
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D058966:Contactins; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D018909:src Homology Domains
C491323:CNTNAP1 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C105177:Cntnap1 protein, rat; D058966:Contactins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins