Role of Membrane Microdomains in Serotonin Receptor Functions

The plasma membrane is a highly compartmentalised organelle containing specialised lipid microdomains or lipid rafts that enable the spatial regulation of signal transduction. Lipid microdomains are enriched in sphingolipids and cholesterol that are arranged in a highly ordered state. Functionally, they contribute to a lesser fluidity compared to the surrounding membrane. Besides their unique lipid composition, these domains are characterised by the accumulation of various signalling molecules, including G protein-coupled receptors (GPCRs) and its downstream effectors. In this way lipid microdomains can integrate a plethora of signalling cascades and thereby modulate the functions of e.g. GPCRs. Here, we provide a short overview about the role of lipid microdomains in the distribution and signalling of GPCRs with particular focus on serotonin receptors. Since recent investigations dealing with lipid microdomain functions revealed the participation of these membrane domains in various pathophysiological processes, we also discuss a possible link between lipid microdomains and serotonin receptor functions in the pathogenesis of depression.