Membrane organization and dynamics of the serotonin1A receptor in live cells

Abstract

The G-protein coupled receptor (GPCR) superfamily is one of the largest classes of molecules involved in signal transduction across the plasma membrane. The serotonin1A receptor is a representative member of the GPCR superfamily and serves as an important target in the development of therapeutic agents for neuropsychiatric disorders such as anxiety and depression. In the context of the pharmacological relevance of the serotonin1A receptor, the membrane organization and dynamics of this receptor in the cellular environment assume relevance. We have highlighted results, obtained from fluorescence microscopy-based approaches, related to domain organization and dynamics of the serotonin1A receptor. A fraction of serotonin 1A receptors displays detergent insolubility, monitored using green fluorescent protein, that increases upon depletion of membrane cholesterol. Fluorescence recovery after photobleaching measurements with varying bleach spot sizes show that lateral diffusion parameters of serotonin1A receptors in normal cells are consistent with models describing diffusion of molecules in a homogenous membrane. Interestingly, these characteristics are altered in cholesterol-depleted cells. Taken together, we conclude that the serotonin1A receptor exhibits dynamic confinement in the cellular plasma membranes. Progress in understanding GPCR organization and dynamics would result in better insight into our overall understanding of GPCR function in health and disease. © 2011 International Society for Neurochemistry.