Neuroligin 1: a splice site-specific ligand for beta-neurexins.
Neurexins are neuronal cell surface proteins with hundreds of isoforms generated by alternative splicing. Here we describe neuroligin 1, a neuronal cell surface protein that is enriched in synaptic plasma membranes and acts as a splice site-specific ligand for beta-neurexins. Neuroligin 1 binds to beta-neurexins only if they lack an insert in the alternatively spliced sequence of the G domain, but not if they contain an insert. The extracellular sequence of neuroligin 1 is composed of a catalytically inactive esterase domain homologous to acetylcholinesterase. In situ hybridization reveals that alternative splicing of neurexins at the site recognized by neuroligin 1 is highly regulated. These findings support a model whereby alternative splicing of neurexins creates a family of cell surface receptors that confers interactive specificity onto their resident neurons.
Ichtchenko
K
K
Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas 75235, USA.
Hata
Y
Y
Nguyen
T
T
Ullrich
B
B
Missler
M
M
Moomaw
C
C
Südhof
T C
TC
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001923:Brain Chemistry; D015816:Cell Adhesion Molecules, Neuronal; D002462:Cell Membrane / Q000737:chemistry; D004950:Esterases / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000737:chemistry; D014018:Tissue Distribution
D015816:Cell Adhesion Molecules, Neuronal; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C093438:neuroligin 1; C086959:neurexin Ibeta; D004950:Esterases