Regulated exocytosis is a complex process that enables the release of informative molecules stored in dedicated vesicles to enable cell-to-cell communication in multicellular organisms. This process begins with vesicle genesis, continues with vesicle transport, culminating in vesicle docking to the plasma membrane and fusion in response to elevated cytosolic calcium, allowing the release of vesicle contents outside the cell, and ends with the recycling of granular components by compensatory endocytosis. Numerous proteins playing a key role in these processes have been identified in recent decades. Although this process involves specific membrane compartments, the role of lipids, major constituents of membranes, and their dynamics between these compartments, remain much less understood.

The aim of this project is to understand the role of contact sites between the endoplasmic reticulum, secretory granules and the plasma membrane in regulating the cycle of exocytosis and endocytosis. In particular, we are studying the dynamics of calcium in the vicinity of exocytosis sites, and the contribution of different forms of phosphatidic acid (PA) during the various stages of exocytosis and their dynamics within these inter-organelle contact sites.

To answer these questions, we are using a molecular toolbox dedicated to the study of PA, based on optogenetic approaches and the use of new forms of PA synthesis that can be activated on demand on the basis of click chemistry.