Olfactory receptor accessory proteins play crucial roles in receptor function and gene choice

Olfaction, or the sense of smell, is perhaps the most complicated and least understood of the five basic senses. Olfactory neurons in the nose can detect and distinguish between tens of thousands of different odor producing substances. They do so by using hundreds of unique sensors called olfactory receptors, each of which responds to a specific type of odor. During development, each olfactory neuron “chooses” to produce only one type of olfactory receptor. Once the neuron recognizes that the functional receptor is being generated and transported to the cell surface, it will stop making all the other olfactory receptors. Chaperone proteins are responsible for transporting many olfactory receptors to the cell surface. To investigate how the loss of these chaperones affects how the olfactory system develops, Sharma et al. studied mice that were unable to produce the olfactory chaperone proteins. In these mice, developing neurons that chose to produce a type of olfactory receptor that depends on chaperone protein transport could not fully shut off other olfactory receptor genes. This led either to the neuron attempting to produce another type of receptor, or the death of the neuron. As a result, more neurons than usual produced receptors that do not require chaperone proteins to transport them to the cell surface. The olfactory neurons therefore produced only a fraction of all possible olfactory receptors, which decreased the ability of the mice to respond to odors. In the future, it will be important to understand what determines whether an olfactory receptor can be transported to the cell membrane in the absence of chaperone proteins. Olfactory receptors are G protein-coupled receptors (GPCRs), which are the largest molecular class of drug targets for cancer and diseases that affect the brain and heart. Thus, results presented by Sharma et al. will also be relevant to researchers who study how GPCR malfunction causes diseases.