Tracking odor receptors

Although the sense of smell is mediated by olfactory G-protein-coupled receptors (GPCRs) that are members of the largest mammalian gene family, the behavior of these receptors is still not well understood. Horst Vogel and his coworkers at the Swiss Federal Institute of Technology, Lausanne, have now used single-molecule fluorescence imaging to track the life cycle of one such human olfactory receptor in living cells (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0603942103). One labeling strategy allowed them to watch the entire receptor lifetime from synthesis to recycling, and a second strategy allowed selective imaging of receptors on the cell surface. The receptors efficiently collect at the cell surface only when they are at low concentrations in the cell. At high concentrations, the receptors collect in intracellular vesicles. The receptors are continuously recycled even in the absence of a ligand, in contrast to the classical model of GPCRs, where receptor internalization is an agonist-dependent process. This mechanism of constant recycling may help maintain sensitivity to odors even during prolonged exposure.