Olfactory receptors are difficult to functionally express in heterologous c
ells. They are typically retained in the endoplasmic reticulum of cells com
monly used for functional expression studies and are only released to the p
lasma membrane in mature cells of the olfactory receptor neuron lineage. A
recently developed olfactory cell line, odora, traffics olfactory receptors
to the plasma membrane when differentiated. We found that undifferentiated
odora cells do not traffic olfactory receptors to their surface, even thou
gh they release the receptors to the Golgi apparatus and endosomes. This be
havior differs from other cell lines tested thus far. Differentiated odora
cells also properly traffic vomeronasal receptors of the VN1 type, which la
ck sequence similarity to olfactory receptors. ODR-4, a protein that is nec
essary for plasma membrane trafficking of a chemosensory receptor in nemato
des, facilitates trafficking of rat olfactory receptor U131 in odora and Ch
inese hamster ovary cells. Olfactory receptor trafficking from the endoplas
mic reticulum to the plasma membrane involves at least two steps whose regu
lation depends on the maturation state of cells in the olfactory receptor n
euron lineage. These results also indicate that some components of the regu
latory mechanism are conserved.