Exocytosis through the Lens

Exocytosis, the process in which material is transported from the cell interior to the extracellular space, proceeds through a complex mechanism. Defects in this process are linked to a number of serious illnesses including diabetes, cancer, and a range of neuropathologies. In neuroendocrine cells, exocytosis involves the fusion of secretory vesicles, carrying signaling molecules, with the plasma membrane through the coordinated interplay of proteins, lipids, and small molecules. This process is highly regulated and occurs in a complex three-dimensional environment within the cell precisely coupled to the stimulus. The study of exocytosis poses significant challenges, involving rapidly changing, nano-scale, protein–protein, and protein–lipid interactions, at specialized sites in the cell. Over the last decade our understanding of neuroendocrine exocytosis has been greatly enhanced by developments in fluorescence microscopy. Modern microscopy encompasses a toolbox of advanced techniques, pushing the limits of sensitivity and resolution, to probe different properties of exocytosis. In more recent years, the development of super-resolution microscopy techniques, side-stepping the limits of optical resolution imposed by the physical properties of light, have started to provide an unparalleled view of exocytosis. In this review we will discuss how advances in fluorescence microscopy are shedding light on the spatial and temporal organization of the exocytotic machinery.