Synaptic Vesicle Exocytosis

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

The function of the nervous system relies on synaptic transmission. Synaptic transmission is mediated by calcium-triggered vesicle fusion, followed by vesicle endocytosis that recycles vesicles. Although significant progress has been made in understanding these processes, much remains unknown. Our goal is to advance the understanding of these synaptic signaling processes. The progress of the last year is described below. I should mention that a large part of our efforts has been devoted to overcoming the severe flooding in December of 2022 in the building. These efforts include room and equipment repair as well as restoring the order of the experiments to the pre-flood level. 1. Recent advances in stimulated emission depletion (STED) microscopy offer an unparalleled avenue to study membrane dynamics of exocytosis, such as fusion pore opening, pore expansion, constriction, and closure. We depict a method of using state-of-the-art STED microscopy to image these membrane dynamics in bovine chromaffin cells. This method can potentially be applied to study other membrane structure dynamics in other cell model systems. 2. Regulated exocytosis, a universal process of eukaryotic cells, involves the merging between the vesicle membrane and the plasma membrane, and plays a key role in cell-to-cell communication, particularly in the release of hormones and neurotransmitters. There are a number of barriers a vesicle needs to pass to discharge vesicle content to the extracellular space. At the pre-fusion site, vesicles need to be transported to the sites on the plasma membrane where the merger may begin. Classically cytoskeleton was considered an important barrier for vesicle translocation and was thought to be disintegrated to allow vesicle access to the plasma membrane. However, it was considered later that cytoskeletal elements may also play a role in the post-fusion stage, promoting the vesicle merger with the plasma membrane and fusion pore expansion. We provided a review of recent progress in exocytosis, particularly related to the question of whether vesicle content discharge is complete or only partial upon the merging of the vesicle membrane with the plasma membrane triggered by Ca2+. 3. Neurotransmitter in vesicles is released through a fusion pore when vesicles fuse with the plasma membrane. The application of advanced electrophysiological techniques to a large nerve terminal, the calyx of Held, has led to direct recordings of individual vesicle fusion and the kinetics of the fusion pore opening process and the fission pore closure process. These studies have revealed two forms of fusion -- full collapse and kiss-and-run. We provide a review of these progresses.