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.

Keywords::

• calcium
• Secretion
• exocytosis
• endocytosis
• fusion pore
• vesicle

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