The Drosophila tumor suppressor gene, dlg, is involved in structural plasticity at a glutamatergic synapse

Synaptic contacts between neurons and their targets are dynamic entities that can change depending on developmental and functional states of the pre- and postsynaptic cell. However, the molecular factors involved in this plasticity have remained largely unknown. We have demonstrated previously that the Drosophila tumor suppressor gene, discs-large (dlg), is expressed at neuromuscular synapses, and is required for normal synapse structure. A family of dlg homologues is also expressed at mammalian synapses, where they interact with the N-methyl-D-aspartate receptor and ion channels. Here, we provide the first demonstration of the involvement of dlg in structural synaptic plasticity during postsynaptic target growth.

We used a temperature-sensitive dlg allele to demonstrate that there are two stages, late embryogenesis and larval stages, at which dlg is necessary for normal formation of synapses. These stages are coincident with dynamic DLG expression at presynaptic sites in the late embryo, and at postsynaptic regions in the larva. Ultrastructural and confocal analyses reveal that Drosophila neuromuscular junctions undergo a dramatic expansion of the postsynaptic apparatus, which is paralleled by target muscle growth. We show that this process of postsynaptic expansion is partially blocked in dlg mutants.

Our results demonstrate that dlg is required during synapse maturation. We show that dlg is involved in the determination of postsynaptic size during target muscle growth. Because motoneuron targets in the larva are continuously growing, synaptic contacts are structurally plastic, undergoing continuous expansion. We conclude that dlg plays an important role in this form of structural synaptic plasticity.