In vivo assembly and trafficking of olfactory Ionotropic Receptors

Ionotropic Receptors (IRs) are a large, divergent subfamily of ionotropic glutamate receptors (iGluRs), with roles in chemosensation, thermosensation and hygrosensation. Analogous to the synaptic targeting mechanisms of their iGluR ancestors, IRs are thought to form complexes of broadly-expressed co-receptors and selectively-expressed 9tuning9 receptors to localise to sensory cilia. While tuning receptors9 extracellular ligand-binding domain (LBD) defines sensory specificity, the role of this domain in co-receptors is unclear. We identify a co-receptor-specific sequence in the LBD, which contains a single N-glycosylation site. Combining molecular genetic and cell biological analyses, we show that this site is dispensable for assembly of IR complexes in olfactory sensory neurons, but essential for endoplasmic reticulum exit of some, but not all, IR complexes. Our data reveal an important role for the IR co-receptor LBD in control of intracellular transport, provide novel insights into the stoichiometry and assembly of IR complexes, and uncover an unexpected heterogeneity in the trafficking regulation of this sensory receptor family.