Trafficking prerogatives of olfactory receptors

Olfactory receptors lead lives of exclusivity and privilege, the monarchs of fiefdoms organized solely to carry out their instructions. Each olfactory sensory neuron expresses one allele of one of ∼1000 olfactory receptor genes. It is thought that olfactory receptor diversity is critical for the ability of animals to detect many thousands of odorants, but supporting functional evidence has been difficult to obtain because olfactory receptors expressed in heterologous cells are typically retained in the endoplasmic reticulum. The membrane trafficking entitlements enjoyed by olfactory receptors appear to be available only in mature olfactory sensory neurons. Evidence is accumulating that cell-type-specific accessory proteins regulate first the exit of olfactory receptors from the endoplasmic reticulum, and then the trafficking of olfactory receptors from post-Golgi compartments to the plasma membrane of the olfactory cilia where the receptors gain access to odorants. Critical olfactory receptor accessory proteins are known only in the nematode Coenorhabditis elegans, where the absence of a novel protein called ODR-4 or a clathrin adaptor, UNC-101, interferes with proper trafficking. Similar functional specifcity also occurs in a parallel chemosensory system, the mammalian vomeronasal organ. Trafficking of the V2R type of vomeronasal receptors is mediated by a vomeronasal-specific family of major histocompatibility complex proteins. Removal of olfactory receptors from the plasma membrane may be regulated in a more conventional fashion because odor stimulation has been linked to receptor phosphorylation, to the function of G-protein coupled receptor kinase 3, and to an increase in vesicles retrieved from the plasma membrane.