Pk17e regulates Drosophila NMJ synapse development and function. Guoli Zhao¹, Li Du², Qifu Wang¹, Yongqing Zhang¹. 1) Institute of Genetics and Developmental Biology, Beijing, Beijing 100101, China; 2) College of Life Science, Hubei University, Wuhan, Hubei 430062, China.

   Synapses are highly specialized intercellular junctions that transmit information between neurons and their targets. Studies on the formation and development of synapses will shed light not only on the physiological neurodevelopment but also the pathogenesis of related neurological diseases. S6K is a family of protein kinases involved in cellular and developmental processes. But its function in neuronal system is not well understood. In this study, we analyzed the function of one member of the S6K family in Drosophila, pk17e, in synaptic development and function, and found that PK17E restrains neuromuscular junction (NMJ) growth and decreases neurotransmission efficiency. pk17e mutants are viable but display distinct NMJ morphological abnormalities, including more synaptic boutons and satellite boutons. pk17e mutations caused significantly reduced synaptic endocytosis at NMJ synapses, as detected using the fluorescent dye FM 1-43 uptake assay. Electrophysiology analysis showed increased mEJP (spontaneous miniature potentials) amplitudes in pk17e mutants. The NMJ overgrowth was caused by enhanced BMP (bone morphogenetic protein) signaling as phosphorylated Mad staining intensity in NMJ synapses was increased in pk17e mutants. Genetic analysis showed that reducing the dose of wit by half in pk17e null background rescued the NMJ overgrowth phenotype. Furthermore, the bouton number was significantly increased in dad and pk17e trans-heterozygotes. Finally, the BMP receptor, Tkv level was increased in pk17e mutants compared with wild-type and the Tkv physically interacts with PK17E in S2 cells. Together, our results demonstrate that pk17e is required for synaptic development via inhibiting BMP signaling.