Lipid dynamics in exocytosis

Abstract

Regulated exocytosis of neurotransmitter- and hormone-containing vesicles underpins neuronal and hormonal communication and relies on a well-orchestrated series of molecular interactions. This in part involves the upstream formation of a complex of SNAREs and associated proteins leading to the eventual fusion of the vesicle membrane with the plasma membrane, a process that enables content release. Although the role of lipids in exocytosis is intuitive, it has long been overlooked at least compared to the extensive work on SNAREs. Here, we will present the latest advances in this rapidly developing field revealing that lipids actually play an active role in exocytosis by focusing on cholesterol, 3'-phosphorylated phosphoinositides and phosphatidic acid.

Fig. 1

Model highlighting the importance of lipids for membrane fusion. PtdIns3P and PtdIns(3,5)P ₂ synthesis at the vesicle membrane positively and negatively regulate vesicle fusion competence, respectively. Cholesterol-rich lipid rafts concentrate PA at or near the exocytotic sites. PtdIns(4,5)P ₂ accumulation at the same location will act synergistically with PA and cholesterol to recruit constituent of the fusion machinery and to create membrane curvature of the inner leaflet of the plasma membrane prior to merger. The Annexin A2 complex could play an important function in the synthesis or maintenance of these lipid microdomains. PtdIns(4,5)P ₂ and PA may also regulate SNARE complex assembly and structure. CAPS potentially mediates the interaction of syntaxin and PtdIns(4,5)P ₂. Other potential regulators of lipid turnover are omitted for clarity