From plant physiology to pharmacology: fusicoccin leaves the leaves

This review highlights 50 years of research on the fungal diterpene fusicoccin, during which the molecule went from a tool in plant physiology research to a pharmacological agent in treating animal diseases. Fusicoccin is a phytotoxic glycosylated diterpene produced by the fungus Phomopsis amygdali, a pathogen of almond and peach plants. Widespread interest in this molecule started when it was discovered that it is capable of causing stomate opening in all higher plants, thereby inducing wilting of leaves. Thereafter, FC became, and still is, a tool in plant physiology, due to its ability to influence a number of fundamental processes, which are dependent on the activation of the plasma membrane H+-ATPase. Molecular studies carried out in the last 20 years clarified details of the mechanism of proton pump stimulation, which involves the fusicoccin-mediated irreversible stabilization of the complex between the H+-ATPase and activatory 14-3-3 proteins. More recently, FC has been shown to influence cellular processes involving 14-3-3 binding to client proteins both in plants and animals. In this review, we report the milestones achieved in more than 50 years of research in plants and highlight recent advances in animals that have allowed this diterpene to be used as a 14-3-3 targeted drug.