Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe mental retardation, motor dysfunction, lack of speech, ataxia and developmental delay. It is caused by the absence of ubiquitin ligase Ube3a which is involved in protein degradation through the ubiquitin-associated proteasome-mediated pathway. Ube3a was also associated with autism spectrum disorder. However, little is known about how the loss-of-function of ube3a results in the pathogenesis of AS. Drosophila has a unique homolog of Ube3a, encoded by ube3a. We found that the number of both total boutons and satellite boutons in ube3a mutants was significantly increased compared with wild type. FM1-43 dye-loading assay showed that ube3a mutants had an endocytosis defect in the NMJ synapses. Furthermore, electrophysiological analysis under high-frequency stimulation showed compromised neurotransmission in ube3a mutant synapses, confirming an insufficient replenishment of synaptic vesicles. These data suggest that ube3a regulates synapse morphology and function. Genetic interaction showed that heterozygous mutants of tkv, encoding the BMP receptor thickveins, rescued the synapse phenotype of ube3a mutants. Immunochemical analysis showed Tkv expression level was increased in ube3a mutants. Co-IP experiments showed that Tkv and Ube3a are present in a complex. Tkv can be ubiquitinated by Ube3a in S2 cells. Interestingly, overexpression of Ube3a also led to an increased number of total boutons and satellite boutons and increased Tkv protein level, suggesting that proper level of Ube3a is critically important for the normal synapse development. Our results suggested that Ube3a regulates BMP signaling pathway to control synapse development. These may partialy accounted for the pathological mechanism of Angelman syndrome.