Vesicular calcium channels as regulators of the exocytotic post-fusion phase

Abstract

Regulated secretion is a fundamental cellular process in many different types of eukaryotic cells with Ca2+-triggered exocytosis taking centre stage. Elevations of the cytoplasmic Ca2+ concentration ([Ca2+]c) regulate multiple steps from vesicle fusion with the plasma membrane to fusion pore dilation and subsequent retrieval of spent vesicles. The general view is that the rise in [Ca2+]c initiates during the pre-fusion stage and either results from Ca2+-influx via Ca2+ channels in the plasma membrane or from release from intracellular Ca2+-stores. However, there is increasing evidence that exocytosis of secretory vesicles triggers additional, localised Ca2+ signals via insertion of vesicle-associated Ca2+ channels into the cell surface. These restricted Ca2+ signals following fusion are ideally suited for regulating the post-fusion fate of individual secretory vesicles. In invertebrates they have been shown to trigger compensatory endocytosis. Recently we have reported that exocytosis of lamellar bodies in alveolar type II epithelial cells results in a localized Ca2+-influx via vesicular P2X4 receptors which regulates fusion pore expansion and vesicle content release. This finding expands the emerging picture that post-fusion Ca2+ entry via vesicle-associated Ca2+ channels plays a central role for regulated exocytosis.