Research Spotlight: Mono- and Poly-unsaturated Phosphatidic Acid Regulates Distinct Steps of Regulated Exocytoses in Neuroendocrine Cells

Posted on February 16, 2021

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Phosphatidic Acid (PA) is interesting due to its known and potential roles in a variety of key biological functions including being a key intermediate in the synthesis of all membrane glycerophospholipids, a contributor to membrane biogenesis, an essential signaling molecule in cell proliferation and cytoskeletal rearrangement, and its participation in endocrine and neuroendocrine exocytosis and synaptic neurotransmission. Mammals can possess up to 40 PA subspecies differing in their fatty acyl chain composition. Awareness of the relevance of PA in cellular function and human pathology is growing and with it, the need for a greater understanding of the precise roles PA subspecies play.

Vitale and his team at Universite de Strasbourg used the well-documented requirement for PA in calcium-regulated exocytosis to explore the role and relevance of PA subspecies in this process. Genetic alteration of phospholipase D (PLD1) was used to dissect the role of PA in sequential stages underlying the exocytotic process in chromaffin cells. They were able to show that PLD1 promotes the synthesis of distinct PA species at the plasma membrane granule docking sites. They also observed that mono- and di-unsaturated PA can regulate the docking of secretory granules and thus the number of secretory events. Omega-3-polyunsaturated PA was observed to regulate fusion pore dynamics and potentially the type or amount of molecule releases per vesicle. Using electron-microscopy, they observed that PA is not only found on the cytosolic leaflet of the plasma membrane in stimulated chromaffin cells, but also on the outer leaflet of the docked secretory granules. This suggests that PA formed in the plasma membrane may diffuse via lipid mixing to the granule membrane at the docking site.

These findings are certainly a large step towards a more complete understanding of the role that PA plays in human health. We look forward to seeing what other accomplishments Nick Vitale and his team can achieve with Avanti’s High-Purity Phosphatidic Acid Lipid Products! Thank you for submitting this work, and we wish you the best of luck with your future research!