Kinetics of M1 muscarinic receptor and G protein signaling to phospholipase C in living cells.

The Journal of General Physiology
Björn H FalkenburgerBertil Hille

Abstract

G protein-coupled receptors (GPCRs) mediate responses to external stimuli in various cell types. Early events, such as the binding of ligand and G proteins to the receptor, nucleotide exchange (NX), and GTPase activity at the Galpha subunit, are common for many different GPCRs. For G(q)-coupled M(1) muscarinic (acetylcholine) receptors (M(1)Rs), we recently measured time courses of intermediate steps in the signaling cascade using Förster resonance energy transfer (FRET). The expression of FRET probes changes the density of signaling molecules. To provide a full quantitative description of M(1)R signaling that includes a simulation of kinetics in native (tsA201) cells, we now determine the density of FRET probes and construct a kinetic model of M(1)R signaling through G(q) to activation of phospholipase C (PLC). Downstream effects on the trace membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) and PIP(2)-dependent KCNQ2/3 current are considered in our companion paper in this issue (Falkenburger et al. 2010. J. Gen. Physiol. doi:10.1085/jgp.200910345). By calibrating their fluorescence intensity, we found that we selected transfected cells for our experiments with approximately 3,000 fluorescently labeled receptors, G...Continue Reading

References

Dec 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·J B Galper, T W Smith
Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M G Vannucchi, P S Goldman-Rakic
Jan 1, 1987·Annual Review of Biophysics and Biophysical Chemistry·L A Sklar
Jun 1, 1988·Cellular and Molecular Neurobiology·L T PotterH E Hanchett
Sep 1, 1994·Biophysical Journal·P A Mahama, J J Linderman
Sep 1, 1994·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R R Neubig
Mar 1, 1993·Biochimica Et Biophysica Acta·E N Pugh, T D Lamb
Jan 5, 1996·The Journal of Biological Chemistry·J R HeplerA G Gilman
Aug 21, 1996·Journal of Theoretical Biology·J M WeissT P Kenakin
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·S Mukhopadhyay, E M Ross
Jul 27, 2000·Current Medicinal Chemistry·M Sautel, G Milligan
Jul 19, 2001·The Journal of Biological Chemistry·T PalancheJ L Galzi
May 14, 2003·Progress in Retinal and Eye Research·Tadao MaedaKrzysztof Palczewski
May 29, 2003·The Journal of Cell Biology·Chang XuLeslie M Loew
Jun 17, 2003·Nature Biotechnology·Jean-Pierre VilardagaMartin J Lohse
Jun 3, 2004·The Journal of General Physiology·Byung-Chang SuhBertil Hille
Jun 26, 2004·Annual Review of Neuroscience·Raul R GainetdinovMarc G Caron
Nov 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Scott J BornheimerShankar Subramaniam
Nov 6, 2004·Science·Seong J An, Wolfhard Almers
Apr 1, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joanna S WinksStephen J Marsh
Sep 1, 2005·The Journal of General Physiology·Lisa F HorowitzBertil Hille
Oct 11, 2005·Visual Neuroscience·R D HamerJ L P Jarvinen
Nov 18, 2005·The EMBO Journal·Peter HeinMoritz Bünemann
Dec 2, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Toru ShinoeToshiya Manabe
Jan 4, 2007·The Journal of Clinical Investigation·Francesca RochaisStefan Engelhardt
Jan 16, 2007·PLoS Computational Biology·Tamara L Kinzer-Ursem, Jennifer J Linderman
Feb 12, 2008·Trends in Pharmacological Sciences·Martin J LohseMoritz Bünemann
Apr 25, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kou QinNevin A Lambert
Aug 22, 2008·PLoS Computational Biology·Marc TurcotteElliott M Ross
Nov 4, 2008·Journal of Molecular Biology·Lijuan He, Kalina Hristova
Dec 3, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Peter Hein, Moritz Bünemann
Jan 27, 2010·The Journal of General Physiology·Björn H FalkenburgerBertil Hille

❮ Previous
Next ❯

Citations

Aug 30, 2011·Nature Chemical Biology·Kou QinNevin A Lambert
Nov 6, 2010·The Journal of Biological Chemistry·Oleg ZaikaMark S Shapiro
Jan 27, 2010·The Journal of General Physiology·Björn H FalkenburgerBertil Hille
Aug 2, 2012·The Journal of General Physiology·Martin KruseBertil Hille
May 1, 2013·The Journal of General Physiology·Eamonn J DicksonBertil Hille
May 1, 2013·The Journal of General Physiology·Björn H FalkenburgerBertil Hille
Feb 22, 2014·Chemistry and Physics of Lipids·Robert V StahelinCary T Frick
Jul 10, 2012·Expert Opinion on Therapeutic Patents·Miroslav Pohanka
Mar 2, 2016·The Journal of General Physiology·Seung-Ryoung JungDuk-Su Koh
Sep 28, 2010·Trends in Biochemical Sciences·Tom D Bunney, Matilda Katan
Jan 5, 2016·Advances in Biological Regulation·Tibor Rohacs
Apr 18, 2014·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Patrick R O'NeillN Gautam
Aug 3, 2013·Channels·Martin Kruse, Bertil Hille
Jul 30, 2014·Frontiers in Cellular Neuroscience·Karim Nagi, Graciela Pineyro
Sep 15, 2010·Journal of Receptor and Signal Transduction Research·Jean-Pierre Vilardaga
Mar 13, 2012·International Journal of Molecular Sciences·Miroslav Pohanka
Oct 4, 2017·The Journal of Biological Chemistry·Raul E GuzmanChristoph Fahlke
Feb 8, 2018·SLAS Technology·Rosa M MellaPatricia Villacé
Apr 13, 2013·Journal of Biomolecular Screening·Paul H TewsonThomas E Hughes
Aug 1, 2013·Physiological Reviews·Tamas Balla
Jul 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Dongjun LiangJeremy M Baskin
Jan 23, 2015·EMBO Reports·Jeeyun ChungPietro De Camilli
May 13, 2014·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Michihiro Tateyama, Yoshihiro Kubo
Jul 15, 2015·Molecular Pharmacology·S RothF J Bruggeman
Jun 4, 2010·The Journal of Physiology·Björn H FalkenburgerBertil Hille
Jun 28, 2017·Proceedings of the National Academy of Sciences of the United States of America·Seung-Ryoung JungBertil Hille
Jul 25, 2020·Scientific Reports·Sam R J HoareLloyd J Bridge
Jun 27, 2019·The Journal of General Physiology·Eric N Senning
Oct 6, 2020·Frontiers in Computational Neuroscience·Adam MergenthalTheodore W Berger
May 11, 2021·Frontiers in Pharmacology·Martin Kruse, Rayne J Whitten
May 10, 2021·Bioorganic & Medicinal Chemistry·Alex G Batrouni, Jeremy M Baskin

❮ Previous
Next ❯

Methods Mentioned

BETA
nucleotide exchange
FRET
chips
flow cytometry
Fluorescence
transfections
GTPase
transfection
fluorescence recovery after photobleaching

Software Mentioned

Virtual Cell
IGOR Pro
FlowJo

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.