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High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity
12:02

High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity

Published on: June 2, 2014

Olfactory receptor interactions with other receptors

Randy A Hall1

  • 1Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. rhall@pharm.emory.edu

Annals of the New York Academy of Sciences
|August 19, 2009
PubMed

Insights

Olfactory receptors (ORs) often fail to reach the cell surface in lab studies. Co-expression with other receptors, like adrenergic or purinergic types, significantly improves OR surface expression and function.

Area of Science:

  • Molecular and Cellular Biology
  • G protein-coupled receptor (GPCR) research
  • Sensory receptor expression systems

Background:

  • Olfactory receptors (ORs) are crucial for smell but challenging to express functionally in heterologous systems.
  • A common issue is endoplasmic reticulum (ER) retention, preventing cell surface localization and limiting study.
  • Understanding OR trafficking is key to unlocking their potential in various research applications.

Purpose of the Study:

  • To investigate methods for improving olfactory receptor M71 surface expression in heterologous cells.
  • To determine if interactions with other G protein-coupled receptors (GPCRs) can overcome trafficking deficits.
  • To explore how co-expressed partner receptors influence M71 signaling pathways.

Main Methods:

  • Utilized heterologous cell expression systems to co-express olfactory receptor M71 with various adrenergic and purinergic receptors.
  • Assessed M71 localization and plasma membrane expression levels using immunofluorescence and cell surface biotinylation assays.
  • Analyzed M71-mediated signaling pathways in response to agonist stimulation, comparing cells with and without partner receptors.

Main Results:

  • Co-expression of olfactory receptor M71 with specific adrenergic and purinergic receptors significantly enhanced M71 trafficking to the plasma membrane.
  • Partner receptor interactions successfully alleviated ER retention, leading to robust surface expression of M71.
  • The choice of partner receptor modulated the downstream signaling pathway coupled by M71 upon agonist binding.

Conclusions:

  • Olfactory receptors can form functional interactions with other GPCRs, such as adrenergic and purinergic receptors.
  • These heterologous interactions are a viable strategy to promote olfactory receptor surface expression and functionality in non-native environments.
  • GPCR partner interactions offer a powerful tool for studying ORs and potentially engineering novel sensory systems.

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