First Author | Missler M | Year | 2003 |
Journal | Nature | Volume | 423 |
Issue | 6943 | Pages | 939-48 |
PubMed ID | 12827191 | Mgi Jnum | J:89452 |
Mgi Id | MGI:3040168 | Doi | 10.1038/nature01755 |
Citation | Missler M, et al. (2003) Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature 423(6943):939-48 |
abstractText | 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. |