Properly formed but improperly localized synaptic specializations in the absence of laminin α4

Precise apposition of pre- to postsynaptic specializations is required for optimal function of chemical synapses, but little is known about how it is achieved. At the skeletal neuromuscular junction, active zones (transmitter release sites) in the nerve terminal lie directly opposite junctional folds in the postsynaptic membrane. Few active zones or junctional folds form in mice lacking the laminin β2 chain, which is normally concentrated in the synaptic cleft β2 and the broadly expressed γ1 chain form heterotrimers with α chains, three of which, α2, α4 and α5, are present in the synaptic cleft. Thus, α2β2γ1, α4β2γ1 and α5β2γ1 heterotrimers are all lost in β2 mutants. In mice lacking laminin α4, active zones and junctional folds form in normal numbers, but are not precisely apposed to each other. Thus, formation and localization of synaptic specializations are regulated separately, and α4β2γ1 (called laminin-9) is critical in the latter process.