Role of Phospholipase D-Derived Phosphatidic Acid in Regulated Exocytosis and Neurological Disease

Lipids play a vital role in numerous cellular functions starting from a structural role as major constituents of membranes to acting as signaling intracellular or extracellular entities. Accordingly, it has been known for decades that lipids, especially those coming from diet, are important to maintain normal physiological functions and good health. On the other side, the exact molecular nature of these beneficial or deleterious lipids, as well as their precise mode of action, is only starting to be unraveled. This recent improvement in our knowledge is largely resulting from novel pharmacological, molecular, cellular, and genetic tools to study lipids in vitro and in vivo. Among these important lipids, phosphatidic acid plays a unique and central role in a great variety of cellular functions. This review will focus on the proposed functions of phosphatidic acid generated by phospholipase D in the last steps of regulated exocytosis with a specific emphasis on hormonal and neurotransmitter release and its potential impact on different neurological diseases.