Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis

Nature. 2003 Jun 26;423(6943):939-48. doi: 10.1038/nature01755.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Stem / cytology
  • Brain Stem / physiology
  • Calcium / metabolism
  • Calcium Channels / physiology*
  • Calcium Signaling
  • Cell Adhesion
  • Cell Adhesion Molecules, Neuronal / physiology
  • Cells, Cultured
  • Evoked Potentials
  • Exocytosis / physiology*
  • Glycoproteins
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neocortex / cytology
  • Neocortex / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neuropeptides
  • Neurotransmitter Agents / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Synapses / physiology*
  • Synaptic Transmission
  • Synaptic Vesicles / physiology*


  • Calcium Channels
  • Cell Adhesion Molecules, Neuronal
  • Glycoproteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Neurotransmitter Agents
  • Recombinant Fusion Proteins
  • neurexin II
  • neurexin IIIalpha
  • neurexophilin
  • Calcium