Determining the role of new molecules in activity-dependent bulk endocytosis

Endocytosis of synaptic vesicle (SV) at the presynaptic terminals is essential for maintaining neurotransmission, particularly during intense neuronal activity. Under these conditions, the dominant SV endocytosis mode is activity-dependent bulk endocytosis (ADBE), suggesting it should perform a central role in brain function. However, determining the physiological role of ADBE in neurotransmission has been hindered due to a limited understanding of its molecular mechanism. This project aims to address this challenge by discovering the selective function of presynaptic molecules in ADBE. This will be achieved by exploiting the recently generated ADBE proteome, which has revealed a series of presynaptic molecules with no currently identified function. The role of these candidate molecules in ADBE and other endocytosis modes will be determined using a palette of live fluorescent imaging assays in primary neuronal cultures from rats. The molecules that are specific to ADBE will to taken forward to determine their molecular mechanism using a series of biochemical interaction studies.