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

The Drosophila tumor suppressor gene lethal (1) discs large (dlg) encodes a protein necessary for normal cell growth in epithelial and brain tissue. It shares high sequence identity to the mammalian synaptic proteins PSD-95 and SAP-70, whose functions are unknown. To determine the localization and role of dig at synapses, we investigated its distribution and the effects of dig mutations on Drosophila neuromuscular junctions. We show that dig immunoreactivity is expressed at one type of glutamatergic synapse and is associated with both presynaptic and postsynaptic 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 indicate that dig is required for normal synaptic structure and offer insights regarding the role of dig homologs at vertebrate synapses.