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Published on: October 2, 2017
Olfactory receptor localization and function: an emerging role for GPCR heterodimerization
Chris Hague1, Randy A Hall, Kenneth P Minneman
1Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Abstract:
Research on olfaction has been fraught with considerable frustration because none of the hundreds of olfactory receptors make it to the cell surface on their own when expressed in heterologous systems. Recent work indicates that the heterodimerization of olfactory receptors with beta2-adrenergic receptors results in surface expression of these G protein-coupled receptors. Similar conclusions--that heterodimerization is essential for surface expression of olfactory receptors--have been drawn from research in Drosophila utilizing completely different knockout and functional approaches. Together these findings may unlock the solution to a problem that has plagued the molecular study of olfaction since the cloning of the first olfactory G protein-coupled receptor over twelve years ago.
Insights
Olfactory receptors require heterodimerization with beta2-adrenergic receptors for cell surface expression. This breakthrough may solve a long-standing problem in olfactory receptor research.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Olfactory receptors (ORs) are crucial for smell but notoriously difficult to express on cell surfaces in isolation.
- Previous attempts to study ORs in heterologous systems have been hindered by their failure to reach the cell surface.
Purpose of the Study:
- To investigate the mechanism behind the cell surface expression of olfactory receptors.
- To identify factors essential for functional olfactory receptor presentation.
Main Methods:
- Studying the co-expression of olfactory receptors with beta2-adrenergic receptors in heterologous systems.
- Utilizing knockout and functional approaches in Drosophila research.
Main Results:
- Heterodimerization of olfactory receptors with beta2-adrenergic receptors facilitates their surface expression.
- Independent research in Drosophila supports the necessity of heterodimerization for OR surface localization.
Conclusions:
- Heterodimerization is essential for the cell surface expression of olfactory receptors.
- These findings offer a potential solution to a persistent challenge in olfactory research, enabling further molecular studies.
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