A synaptic laminin-calcium channel interaction organizes active zones in motor nerve terminals.
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.
Nishimune
Hiroshi
H
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Sanes
Joshua R
JR
Carlson
Steven S
SS
D000818:Animals; D001665:Binding Sites; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D007797:Laminin / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000166:cytology / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D017474:Receptors, Laminin / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism
D020864:Calcium Channels, N-Type; D007797:Laminin; D018377:Neurotransmitter Agents; D021122:Protein Subunits; D017474:Receptors, Laminin; C404084:laminin 9; C058783:laminin beta2