Functional Profiling of a Human Odorant Receptor Using Olfactory Cilia Links its Activation to Odor Quality
The mechanism governing singular odorant receptor (OR) gene choice restricts each olfactory sensory neuron (OSN) to expressing a single OR allele from a repertoire of more than 1,100 receptor genes. Consequently, only a small fraction of OSNs express any given OR, limiting studies of OR function, axonal wiring, and odor coding. Here, we show that multimerizing a 21-bp homeodomain enhancer…
A study has uncovered a key mechanism behind how a specific human odorant receptor (OR) gene is chosen for expression in olfactory sensory neurons (OSNs). Each OSN is programmed to express just one OR allele out of over 1,100 possibilities. This study demonstrates that a 21-base pair homeodomain enhancer, when repeated nine times, significantly raises the chance that a single OR10G4 gene will be selected for expression.
An engineered single-copy Olfr151 minigene with this powerful enhancer drove OR10G4 expression in about 75% of OSNs. This increase in OR10G4-expressing cilia allowed for extremely sensitive screening of odorant ligands using CELIA (Cilia-based Evaluation of Ligands and receptor InterActions). Testing various guaiacol derivatives showed that activation of OR10G4 correlated well with published human psychophysical responses to these compounds.
Interestingly, while OR10G4 responded to smoky odors, it did not respond strongly to common vanilla odors. This suggests that the receptor's main role may not be in vanilla perception. Instead, the findings indicate a direct link between the activation of a single human OR and a specific perceptual dimension of odor quality. The study also shows that by manipulating cis-regulatory elements, researchers can decode the molecular basis of human odor perception.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
