Muscarinic receptors as enhancers for odorant receptor functional expression

Value Proposition

The mammalian sense of smell is afforded by a highly complex system of specialized neurons expressing a multitude of odorant receptors (ORs). Even though these ORs make up the largest family of G-protein coupled receptors, very little progress has been made in understanding the specific molecules sensed by any individual receptor. This lack of understanding is due, in large part, to an inability to achieve sufficient expression and activation of these receptors in an experimentally-tractable heterologous cell type. This technology addresses this significant technical challenge by providing a cell line-based system for evaluating activity of a given OR in response to a ligand, thereby enabling large-scale screening for defining OR specificity.

Technology

This technology solves the problem of weak OR activity in heterologous cells by co-expressing a novel interacting protein, the M3 muscarinic receptor (M3), which results in enhanced cell signaling in response to known OR ligands. In this system, OR activity is reliably measured using an engineered luciferase reporter system. This technology was tested in the Hana3A cell line, where co-expression of M3 resulted in enhanced OR signaling across over 30 distinct mammalian ORs.

Other applications

• Precise detection of odorous compounds for industrial quality control (i.e. food manufacturing)
• Screening of novel compounds for enhancing / reducing OR activity for therapeutic
• Development of novel compounds designed to stimulate specific odor / taste receptors for food and beverage products (i.e. artificial sweeteners, bitterness-reducing additives, etc.)

Advantanges

Current methods for assessing OR activity / specificity rely on increasing surface expression of the receptor. Such methods are of variable success for individual receptors, and do not address poor signaling activity even with increased surface expression of the receptor. This technology overcomes this limitation, by promoting signaling without altering surface receptor expression. Importantly, this technology can be used in combination with such previous methods to provide maximal sensitivity.