"Olfactory receptors (ORs) are synthesised in endoplasmic reticulum of the olfactory neurons, trafficked to the cell surface membrane and transported to the tip of the olfactory cilium, where they bind with odorants. Various accessory proteins are required for proper targeting of different ORs to the cell membrane. ODR-4, the first accessory protein described, was identified in Caenorhabditis elegans as a mutant defective for odorant response. In the AWA and AWC neurons of C. elegans, ODR-4 protein (CeODR-4) is required for expression and transport of a subset of ORs, including the diacetyl-specific ODR-10 to ciliary membranes. Orthologs of ODR-4 have been identified from human (hODR-4) and other organisms. The relationship between CeODR-4 and other accessory proteins, and the molecular mechanism of CeODR-4 function are largely unknown. In this study, to investigate whether they are functional homologs of CeODR-4, we transformed C. elegans
odr-4 mutants with expression constructs for four ODR-4 homologs from different origins. There were expressed under the control of the ODR-10 promoter which targets expression to the paired AWA neurons. Only the
odr-4 construct from the closely related nematode C. briggsae fully complemented the
odr-4-mutation in chemotaxis assays. This confirms the high level of functional homology between CeODR-4 and CbODR-4. Other accessory proteins, REEP1, RTP1 and RTP2 from rat, OR83b from insect and hODR-4 were unable to complement the
odr-4-mutation. We also explored the molecular mechanisms of ODR-4 function by generating truncated and chimaeric ODR-4 proteins. The two truncated proteins did not complement the
odr-4 mutant. A chimaera comprising the cytoplasmic domain of hODR-4 and the transmembrane domain of CeODR-4 complemented the
odr-4 mutant. However, a chimaera with the cytoplasmic domain of CeODR-4 and the transmembrane domain of hODR-4 did not complement the
odr-4 mutant. In conclusion, it appears that the conserved transmembrane domain of CeODR-4 is critical for trafficking a subset of odorant receptors in C. elegans."