title: Neurexin mediates the assembly of presynaptic terminals.
abstract: Neurexins are a large family of proteins that act as neuronal cell-surface receptors. The function and localization of the various neurexins, however, have not yet been clarified. Beta-neurexins are candidate receptors for neuroligin-1, a postsynaptic membrane protein that can trigger synapse formation at axon contacts. Here we report that neurexins are concentrated at synapses and that purified neuroligin is sufficient to cluster neurexin and to induce presynaptic differentiation. Oligomerization of neuroligin is required for its function, and we find that beta-neurexin clustering is sufficient to trigger the recruitment of synaptic vesicles through interactions that require the cytoplasmic domain of neurexin. We propose a two-step model in which postsynaptic neuroligin multimers initially cluster axonal neurexins. In response to this clustering, neurexins nucleate the assembly of a cytoplasmic scaffold to which the exocytotic apparatus is recruited.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, 271 LSA, California 94720, USA.
authors.forename: Camin
authors.initials: C
authors.lastname: Dean
authors.forename: Francisco G
authors.initials: FG
authors.lastname: Scholl
authors.forename: Jenny
authors.initials: J
authors.lastname: Choih
authors.forename: Shannon
authors.initials: S
authors.lastname: DeMaria
authors.forename: James
authors.initials: J
authors.lastname: Berger
authors.forename: Ehud
authors.initials: E
authors.lastname: Isacoff
authors.forename: Peter
authors.initials: P
authors.lastname: Scheiffele
mesh_terms: D000409:Alanine / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D002449:Cell Aggregation / Q000235:genetics / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D002645:Chickens; D002795:Choline O-Acetyltransferase / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods; D007668:Kidney; D008051:Lipid Bilayers / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016716:PC12 Cells; D011149:Pons / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D050683:R-SNARE Proteins; D012324:RNA-Dependent RNA Polymerase / Q000276:immunology / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship; D013569:Synapses / Q000235:genetics / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism; D050857:Synaptotagmins; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008051:Lipid Bilayers; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016271:Proto-Oncogene Proteins c-myc; D050683:R-SNARE Proteins; D018091:Receptors, AMPA; D011994:Recombinant Proteins; D014764:Viral Proteins; C104723:glutamate receptor ionotropic, AMPA 3; C093438:neuroligin 1; C033652:postsynaptic density proteins; D050857:Synaptotagmins; C086959:neurexin Ibeta; D002795:Choline O-Acetyltransferase; C040530:L protein, vesicular stomatitis virus; D012324:RNA-Dependent RNA Polymerase; D000409:Alanine; C104722:glutamate receptor ionotropic, AMPA 2