Drosophila Neuroligin 1 Promotes Growth and Postsynaptic Differentiation at Glutamatergic Neuromuscular Junctions

Precise apposition of presynaptic and postsynaptic domains is a fundamental property of all neuronal circuits. Experiments in vitro suggest that Neuroligins and Neurexins function as key regulatory proteins in this process. In a genetic screen, we recovered several mutant alleles of Drosophila neuroligin 1 (dnIg1) that cause a severe reduction in bouton numbers at neuromuscular junctions (NMJs). In accord with reduced synapse numbers, these NMJs show reduced synaptic transmission. Moreover, lack of postsynaptic DNIg1 leads to deficits in the accumulation of postsynaptic glutamate receptors, scaffold proteins, and subsynaptic membranes, while increased DNIg1 triggers ectopic postsynaptic differentiation via its cytoplasmic domain. DNIg1 forms discrete clusters adjacent to postsynaptic densities. Formation of these clusters depends on presynaptic Drosophila Neurexin (DNrx). However, DNrx binding is not an absolute requirement for DNIg1 function. Instead, other signaling components are likely involved in DNIg1 transsynaptic functions, with essential interactions organized by the DNIg1 extracellular domain but also by the cytoplasmic domain.