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

• Published in: Neuron (Cambridge, Mass.) Vol. 55; no. 5; pp. 741 - 755
• Main Authors: Li, Jingjun, Ashley, James, Budnik, Vivian, Bhat, Manzoor A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.09.2007; Elsevier Limited
• Subjects: Animals; Cell adhesion & migration; Cell Adhesion - genetics; Cell Adhesion Molecules, Neuronal - genetics; Cell Adhesion Molecules, Neuronal - metabolism; Cell culture; Cell Differentiation - genetics; CELLBIO; DEVBIO; Drosophila melanogaster - embryology; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Gene Expression Regulation, Developmental - genetics; Genes; Genomes; Insects; Mammals; Microscopy; Molecular Sequence Data; MOLNEURO; Motor Neurons - metabolism; Motor Neurons - ultrastructure; Mutation - genetics; Neuromuscular Junction - abnormalities; Neuromuscular Junction - growth & development; Neuromuscular Junction - metabolism; Neurosciences; Presynaptic Terminals - metabolism; Presynaptic Terminals - ultrastructure; Proteins; Sequence Homology, Amino Acid; Software; Statistical analysis; Synapses - genetics; Synapses - metabolism; Synapses - ultrastructure; Synaptic Membranes - genetics; Synaptic Membranes - metabolism; Synaptic Membranes - ultrastructure; Synaptic Transmission - genetics; CELLBIO; DEVBIO; MOLNEURO
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2007.08.002

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.