A synaptic laminin-calcium channel interaction organizes active zones in motor nerve terminals

Nature. 2004 Dec 2;432(7017):580-7. doi: 10.1038/nature03112.


Synapse formation requires the differentiation of a functional nerve terminal opposite a specialized postsynaptic membrane. Here, we show that laminin beta2, a component of the synaptic cleft at the neuromuscular junction, binds directly to calcium channels that are required for neurotransmitter release from motor nerve terminals. This interaction leads to clustering of channels, which in turn recruit other presynaptic components. Perturbation of this interaction in vivo results in disassembly of neurotransmitter release sites, resembling defects previously observed in an autoimmune neuromuscular disorder, Lambert-Eaton myasthenic syndrome. These results identify an extracellular ligand of the voltage-gated calcium channel as well as a new laminin receptor. They also suggest a model for the development of nerve terminals, and provide clues to the pathogenesis of a synaptic disease.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Calcium Channels, N-Type / chemistry
  • Calcium Channels, N-Type / deficiency
  • Calcium Channels, N-Type / genetics
  • Calcium Channels, N-Type / metabolism*
  • Cells, Cultured
  • Laminin / chemistry
  • Laminin / deficiency
  • Laminin / genetics
  • Laminin / metabolism*
  • Mice
  • Motor Neurons / cytology*
  • Motor Neurons / metabolism*
  • Mutation / genetics
  • Neuromuscular Junction / cytology
  • Neuromuscular Junction / metabolism
  • Neurotransmitter Agents / metabolism
  • Presynaptic Terminals / metabolism
  • Protein Binding
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Receptors, Laminin / metabolism
  • Synapses / metabolism*
  • Synaptic Vesicles / metabolism


  • Calcium Channels, N-Type
  • Laminin
  • Neurotransmitter Agents
  • Protein Subunits
  • Receptors, Laminin
  • laminin 9
  • voltage-dependent calcium channel (P-Q type)
  • laminin beta2