The nematode C. elegans provides a powerful model system for exploring the molecular basis of synaptogenesis and neurotransmission. However, the lack of direct functional assays for release processes has largely prevented an in depth understanding of the mechanism of vesicular exocytosis and endocytosis in C. elegans. For the first time, Professor Tao Xu’s group established a high spatial-temporal method to monitor secretion from neurons. They developed direct electrophysiological assays, including membrane capacitance and amperometry measurements, in primary cultured C. elegans neurons. In addition, they succeeded in monitoring the docking and fusion of single dense core vesicles (DCVs) employing total internal reflection fluorescence microscopy. Using these approaches and mutant perturbation analysis, they provided direct evidence that UNC-31 is required for the docking of DCVs at the plasma membrane. Interestingly, they discovered that the defect in DCV docking caused by the UNC-31 mutation can be fully rescued by PKA activation. They also demonstrated that UNC-31 is required for UNC-13-mediated augmentation of DCV exocytosis. This work represented a significant technical advance in the analysis of regulated exocytosis in an important genetic system, C.elegans, and also uncovered new insights into the mechanisms underlying secretion.

This work was published on Neuron (2007,56(4):657-669).