Structures, alternative splicing, and neurexin binding of multiple neuroligins.
Neuroligin 1 is a neuronal cell surface protein that binds to a subset of neurexins, polymorphic cell surface proteins that are also localized on neurons (Ichtchenko, K., Hata, Y., Nguyen, T., Ullrich, B., Missler, M., Moomaw, C., and Südhof, T. C. (1995) Cell 81, 435-443). We now describe two novel neuroligins called neuroligins 2 and 3 that are similar in structure and sequence to neuroligin 1. All neuroligins contain an N-terminal hydrophobic sequence with the characteristics of a cleaved signal peptide followed by a large esterase homology domain, a highly conserved single transmembrane region, and a short cytoplasmic domain. The three neuroligins are alternatively spliced at the same position and are expressed at high levels only in brain. Binding studies demonstrate that all three neuroligins bind to beta-neurexins both as native brain proteins and as recombinant proteins. Tight binding of the three neuroligins to beta-neurexins is observed only for beta-neurexins lacking an insert in splice site 4. Thus, neuroligins constitute a multigene family of brain-specific proteins with distinct isoforms that may have overlapping functions in mediating recognition processes between neurons.
Ichtchenko
K
K
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Nguyen
T
T
Südhof
T C
TC
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal; D002450:Cell Communication; D002460:Cell Line; D018076:DNA, Complementary; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
D015816:Cell Adhesion Molecules, Neuronal; D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C093175:neurexin II; C098003:neuroligin 2; C098004:neuroligin 3