Institute of Life Sciences, the Collaborative Innovation Center for Brain Science, Southeast University, Nanjing, China; The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
Yichen Sun
Institute of Life Sciences, the Collaborative Innovation Center for Brain Science, Southeast University, Nanjing, China
Menglong Rui
Institute of Life Sciences, the Collaborative Innovation Center for Brain Science, Southeast University, Nanjing, China
Yan Zhuang
Institute of Life Sciences, the Collaborative Innovation Center for Brain Science, Southeast University, Nanjing, China
Huihui Lv
The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China
Institute of Life Sciences, the Collaborative Innovation Center for Brain Science, Southeast University, Nanjing, China; The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
Institute of Life Sciences, the Collaborative Innovation Center for Brain Science, Southeast University, Nanjing, China; Neurosciences and Mental Health Program, The Hospital for Sick Children, University of Toronto, Ontario, Canada
Institute of Life Sciences, the Collaborative Innovation Center for Brain Science, Southeast University, Nanjing, China; The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
Neuroligins are postsynaptic adhesion molecules that are essential for postsynaptic specialization and synaptic function. But the underlying molecular mechanisms of neuroligin functions remain unclear. We found that Drosophila Neuroligin 1 (DNlg1) regulates synaptic structure and function through WAVE regulatory complex (WRC)-mediated postsynaptic actin reorganization. The disruption of DNlg1, DNlg2, or their presynaptic partner neurexin (DNrx) led to a dramatic decrease in the amount of F-actin. Further study showed that DNlg1, but not DNlg2 or DNlg3, directly interacts with the WRC via its C-terminal interacting receptor sequence. That interaction is required to recruit WRC to the postsynaptic membrane to promote F-actin assembly. Furthermore, the interaction between DNlg1 and the WRC is essential for DNlg1 to rescue the morphological and electrophysiological defects in dnlg1 mutants. Our results reveal a novel mechanism by which the DNrx-DNlg1 trans-synaptic interaction coordinates structural and functional properties at the neuromuscular junction.
