THE DROSOPHILA TUMOR-SUPPRESSOR GENE, DIG, IS INVOLVED IN STRUCTURAL PLASTICITY AT A GLUTAMATERGIC SYNAPSE

Background: Synaptic contacts between neurons and their targets are dy namic entities that can change depending on developmental and function al states of the pre- and postsynaptic cell. However, the molecular fa ctors involved in this plasticity have remained largely unknown. We ha ve demonstrated previously that the Drosophila tumor suppressor gene, discs-large (dlg), is expressed at neuromuscular synapses, and is requ ired for normal synapse structure. A family of dig 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 dem onstration of the involvement of dig in structural synaptic plasticity during postsynaptic target growth. Results: We used a temperature-sen sitive dig allele to demonstrate that there are two stages, late embry ogenesis and larval stages, at which dig is necessary for normal forma tion of synapses. These stages are coincident with dynamic DLG express ion at presynaptic sites in the late embryo, and at postsynaptic regio ns in the larva. Ultrastructural and confocal analyses reveal that Dro sophila neuromuscular junctions undergo a dramatic expansion of the po stsynaptic apparatus, which is paralleled by target muscle growth. We show that this process of postsynaptic expansion is partially blocked in dig mutants. Conclusions: Our results demonstrate that dig is requi red during synapse maturation. We show that dig is involved in the det ermination of postsynaptic size during target muscle growth. Because m otorneuron targets in the larva are continuously growing, synaptic con tacts are structurally plastic, undergoing continuous expansion. We co nclude that dig plays an important role in this form of structural syn aptic plasticity.