Crucial Role of Drosophila Neurexin in Proper Active Zone Apposition to Postsynaptic Densities, Synaptic Growth, and Synaptic Transmission

Neurexins have been proposed to function as major mediators of the coordinated pre- and postsynaptic apposition. However, key evidence for this role in vivo has been lacking, particularly due to gene redundancy. Here, we have obtained null mutations in the single Drosophila neurexin gene (dnrx). dnrx loss of function prevents the normal proliferation of synaptic boutons at glutamatergic neuromuscular junctions, while dnrx gain of function in neurons has the opposite effect. DNRX mostly localizes to the active zone of presynaptic terminals. Conspicuously, dnrx null mutants display striking defects in synaptic ultrastructure, with the presence of detachments between pre- and postsynaptic membranes, abnormally long active zones, and increased number of T bars. These abnormalities result in corresponding alterations in synaptic transmission with reduced quantal content. Together, our results provide compelling evidence for an in vivo role of neurexins in the modulation of synaptic architecture and adhesive interactions between pre- and postsynaptic compartments.