Cholesterol and synaptic vesicle exocytosis

Lipids may affect synaptic function in at least two ways: by acting as ligands for effector proteins (e.g. phosphatidylinositol (4,5) bisphosphate, diacylglycerol-mediated signalling) or by modifying the physicochemical properties and molecular organisation of synaptic membranes. One that acts in the latter manner is cholesterol, an essential structural component of plasma membranes that is largely enriched in the membranes of synapses and synaptic vesicles, in which it may be involved in lipid-lipid and protein-lipid interactions. Cholesterol is an important constituent of the "membrane rafts" that may play a role in recruiting and organising the specific proteins of the exocytic pathways. Furthermore, many synaptic proteins bind directly to cholesterol. The regulation of cholesterol and lipid levels may therefore influence the specific interactions and activity of synaptic proteins, and have a strong impact on synaptic functions.