Neurexin Regulates Synaptic Growth Via Gbb Signaling Pathway At Drosophila Neuromuscular Junction

Synaptogenesis is the formation of synapses between neurons in the nervous system. The formation of correct synaptic connection can make the information transmission reliable. Cell adhesion molecules are believed to play the key role in maintaining synaptic integrity/stability, target recognition, synaptic differentiation and plasticity regulation. Neurexins(Nrxs) are cell adhesion molecules required for synaptic formation and differentiation. Previous researches have shown that the normal proliferation of synaptic boutons at glutamatergic neuromuscular junction is prevented in dnrx loss of function mutants. However, the mechanism remains poorly understood. Here, we report that Drosophila Neurexin regulates Gbb signaling pathway to control synaptic growth. Consistently, we find that neuronal overexpression of neurexin can increase synaptic boutons and branches, and the synaptic growth is dosage-dependent on Neurexin. Moreover, the intracellular domain of Dnrx is critical for such process. At the first time, we showed that P-mad, as the readout of Gbb signaling, was dramatically decreased in dnrx mutants and increased in dnrx overexpression flies. Simultaneously, lack of dnrx leads to significantly reduced tkv-GFP fluorescent intensity. Furthermore, Neurexin-induced synaptic overgrowth can be blocked in wit mutants. Taken together, our results reveal a role for neurexin in regulating Gbb signaling pathway to control synaptic growth in Drosophila neuromuscular junction.