Lipids in Regulated Exocytosis: What are They Doing?

Abstract

The regulated secretory pathway in neuroendocrine cells ends with the release of hormones and neurotransmitters following a rise in cytosolic calcium. This process known as regulated exocytosis involves the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, the synaptic vesicle VAMP (synaptobrevin), and the plasma membrane proteins syntaxin and SNAP-25. Although there is much evidence suggesting that SNARE proteins play a key role in the fusion machinery, other cellular elements regulating the kinetics, the extent of fusion, and the preparation of vesicle for release have received less attention. Among those factors, lipids have also been proposed to play important functions both at the level of secretory vesicle recruitment and late membrane fusion steps. Here, we will review the latest evidence supporting the concept of the fusogenic activity of lipids, and also discuss how this may be achieved. These possibilities include the recruitment and sequestration of the components of the exocytotic machinery, regulation of protein function, and direct effects on membrane topology.

Keywords: cholesterol; chromaffin cell; exocytosis; membrane fusion; phosphatidic acids; phosphoinositides.

Figure 1

Model highlighting the importance of lipids for membrane fusion. Exocytotic sites defined as cholesterol, GM1, PtdIns(4,5)P₂, and PA enriched microdomains recruit constituents of the docking/fusion machinery and create membrane curvature of the inner leaflet of the plasma membrane prior to promote membrane merging. PtdIns(4,5)P₂ and PA may also regulate SNARE complex assembly and structure.