THE DROSOPHILA TUMOR-SUPPRESSOR GENE DLG IS REQUIRED FOR NORMAL SYNAPTIC BOUTON STRUCTURE

The Drosophila tumor suppressor gene lethal (1) discs large (dlg) enco des a protein necessary for normal cell growth in epithelial and brain tissue. It shares high sequence identity to the mammalian synaptic pr oteins PSD-95 and SAP-70, whose functions are unknown. To determine th e localization and role of dig at synapses, we investigated its distri bution and the effects of dig mutations on Drosophila neuromuscular ju nctions. We show that dig immunoreactivity is expressed at one type of glutamatergic synapse and is associated with both presynaptic and pos tsynaptic membranes. Mutations in dig alter the expression of dig and cause striking changes in the structure of the subsynaptic reticulum, a postsynaptic specialization at these synapses. These results indicat e that dig is required for normal synaptic structure and offer insight s regarding the role of dig homologs at vertebrate synapses.