Endoplasmic reticulum degradation impedes olfactory G-protein coupled receptor functional expression

BMC Cell Biology
Min LuBryan D Moyer

Abstract

Research on olfactory G-protein coupled receptors (GPCRs) has been severely impeded by poor functional expression in heterologous systems. Previously, we demonstrated that inefficient olfactory receptor (OR) expression at the plasma membrane is attributable, in part, to degradation of endoplasmic reticulum (ER)-retained ORs by the ubiquitin-proteasome system and sequestration of ORs in ER aggregates that are degraded by autophagy. Thus, experiments were performed to test the hypothesis that attenuation of ER degradation improves OR functional expression in heterologous cells. To develop means to increase the functional expression of ORs, we devised an approach to measure activation of the mOREG OR (Unigene # Mm.196680; Olfr73) through coupling to an olfactory cyclic nucleotide-gated cation channel (CNG). This system, which utilizes signal transduction machinery coupled to OR activation in native olfactory sensory neurons, was used to demonstrate that degradation, both by the ubiquitin-proteasome system and autophagy, limits mOREG functional expression. The stimulatory effects of proteasome and autophagy inhibitors on mOREG function required export from the ER and trafficking through the biosynthetic pathway. These findings demo...Continue Reading

References

Mar 1, 1992·The Journal of Cell Biology·R D KlausnerJ Lippincott-Schwartz
May 7, 1990·Biochimica Et Biophysica Acta·H H MollenhauerL D Rowe
Mar 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·P O Seglen, P B Gordon
Jan 31, 1998·Science·H ZhaoS Firestein
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·T LiE L Berson
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·K TouharaT Haga
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·L MengC M Crews
Oct 3, 1999·The Journal of Biological Chemistry·R JockersS Marullo
Apr 13, 2000·Cell·J ChandrashekarN J Ryba
Dec 21, 2000·Trends in Pharmacological Sciences·J P MorelloM Bouvier
Mar 21, 2001·EMBO Reports·R R Kopito, R Sitia
Sep 15, 2001·Nature·S Firestein
Nov 1, 2001·Nature Neuroscience·P Mombaerts
Feb 5, 2002·Annual Review of Physiology·Gabriele V Ronnett, Cheil Moon
Mar 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Xiaodong LiElliot Adler
Apr 30, 2002·Human Molecular Genetics·Brinda RavikumarDavid C Rubinsztein
Jun 28, 2002·Physiological Reviews·U Benjamin Kaupp, Reinhard Seifert
Apr 25, 2003·Canadian Journal of Physiology and Pharmacology·Fernand GobeilSylvain Chemtob
May 21, 2003·The Journal of Biological Chemistry·Benoit BoivinBruce G Allen
May 28, 2003·Biochemical and Biophysical Research Communications·Sayako KatadaKazushige Touhara
Sep 23, 2003·Neuroreport·Timothy S McClintock, Neeraja Sammeta
Oct 3, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sylwester ChybJohn R Carlson
Jan 16, 2004·Trends in Pharmacological Sciences·Richard J H Wojcikiewicz
Mar 23, 2004·Nature Reviews. Neuroscience·Peter Mombaerts
Apr 9, 2004·The Journal of Biological Chemistry·Kezhong Zhang, Randal J Kaufman
Jun 12, 2004·American Journal of Respiratory Cell and Molecular Biology·Meerana LimPamela L Zeitlin
Sep 3, 2004·Journal of Neurochemistry·Sayako KatadaKazushige Touhara
Aug 27, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sunitha RangarajuLucia Notterpek

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Citations

Oct 6, 2007·Molecular Neurobiology·Bettina Malnic
Apr 16, 2014·The Journal of General Physiology·Zita PeterlinMatthew E Rogers
Apr 12, 2006·Journal of Neurochemistry·Tatjana AbaffyCharles W Luetje
Sep 19, 2006·Life Sciences·Kathleen Van CraenenbroeckPeter Vanhoenacker
Feb 23, 2012·Scientific Reports·Karolina CorinShuguang Zhang
Feb 15, 2018·Physiological Reviews·Ya-Xiong Tao, P Michael Conn
Jan 27, 2009·Journal of Neurochemistry·Sarah E Repicky, Charles W Luetje
Aug 19, 2009·Annals of the New York Academy of Sciences·Hiroaki MatsunamiSandeepa Dey
Aug 13, 2015·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Blythe D Shepard, Jennifer L Pluznick
May 20, 2005·The Journal of Biological Chemistry·E Maritta PietiläUlla E Petäjä-Repo
Apr 12, 2012·Molecular BioSystems·Karolina CorinShuguang Zhang
Jan 18, 2018·Chemical Senses·Maik BehrensSimone Weyand
Aug 29, 2021·BMC Biology·Simona Francia, Claudia Lodovichi
Dec 9, 2008·Molecular and Cellular Endocrinology·P Michael Conn, Jo Ann Janovick
Mar 25, 2009·Trends in Pharmacological Sciences·P Michael Conn, Jo Ann Janovick
Mar 12, 2005·Science·Sylvia Curtis HewittKenneth S Korach

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Methods Mentioned

BETA
transfection
polyubiquitination
biosensor
fluorescence microscopy

Software Mentioned

GraphPad Prism
Imaging Workbench

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