title: Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis.
abstract: Synapses are specialized intercellular junctions in which cell adhesion molecules connect the presynaptic machinery for neurotransmitter release to the postsynaptic machinery for receptor signalling. Neurotransmitter release requires the presynaptic co-assembly of Ca2+ channels with the secretory apparatus, but little is known about how synaptic components are organized. Alpha-neurexins, a family of >1,000 presynaptic cell-surface proteins encoded by three genes, link the pre- and postsynaptic compartments of synapses by binding extracellularly to postsynaptic cell adhesion molecules and intracellularly to presynaptic PDZ domain proteins. Using triple-knockout mice, we show that alpha-neurexins are not required for synapse formation, but are essential for Ca2+-triggered neurotransmitter release. Neurotransmitter release is impaired because synaptic Ca2+ channel function is markedly reduced, although the number of cell-surface Ca2+ channels appears normal. These data suggest that alpha-neurexins organize presynaptic terminals by functionally coupling Ca2+ channels to the presynaptic machinery.
authors.affiliation: Center for Basic Neuroscience, Department of Molecular Genetics, Dallas, Texas 75390-9111, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Missler
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.forename: Astrid
authors.initials: A
authors.lastname: Rohlmann
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kattenstroth
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hammer
authors.forename: Kurt
authors.initials: K
authors.lastname: Gottmann
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology; D002478:Cells, Cultured; D005071:Evoked Potentials; D005089:Exocytosis / Q000502:physiology*; D006023:Glycoproteins; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D015816:Cell Adhesion Molecules, Neuronal; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D011993:Recombinant Fusion Proteins; C093175:neurexin II; C082354:neurexin IIIalpha; C112162:neurexophilin; D002118:Calcium