Heterotrimeric G Protein Subunit Gαq Is a Master Switch for Gβγ-Mediated Calcium Mobilization by Gi-Coupled GPCRs.

Molecular Cell
Eva Marie PfeilEvi Kostenis

Abstract

Mechanisms that control mobilization of cytosolic calcium [Ca2+]i are key for regulation of numerous eukaryotic cell functions. One such paradigmatic mechanism involves activation of phospholipase Cβ (PLCβ) enzymes by G protein βγ subunits from activated Gαi-Gβγ heterotrimers. Here, we report identification of a master switch to enable this control for PLCβ enzymes in living cells. We find that the Gαi-Gβγ-PLCβ-Ca2+ signaling module is entirely dependent on the presence of active Gαq. If Gαq is pharmacologically inhibited or genetically ablated, Gβγ can bind to PLCβ but does not elicit Ca2+ signals. Removal of an auto-inhibitory linker that occludes the active site of the enzyme is required and sufficient to empower "stand-alone control" of PLCβ by Gβγ. This dependence of Gi-Gβγ-Ca2+ on Gαq places an entire signaling branch of G-protein-coupled receptors (GPCRs) under hierarchical control of Gq and changes our understanding of how Gi-GPCRs trigger [Ca2+]i via PLCβ enzymes.

References

Dec 1, 1992·Trends in Biochemical Sciences·P C Sternweis, A V Smrcka
Jun 15, 1992·European Journal of Biochemistry·M CampsP Gierschik
Oct 1, 1981·Physiological Reviews·C B Wollheim, G W Sharp
Jan 1, 1995·The Journal of General Physiology·S S WangS H Thompson
Aug 1, 1994·The International Journal of Biochemistry·J M Dickenson, S J Hill
Jun 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·D WuM I Simon
Apr 2, 1996·Proceedings of the National Academy of Sciences of the United States of America·Y KuangD Wu
Nov 1, 1996·Nature Medicine·B A Premack, T J Schall
Sep 20, 1997·Nature·S OffermannsM I Simon
Apr 29, 1998·Nature·M Baggiolini
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·B LeeR W Doms
Jun 22, 1999·Current Opinion in Immunology·S Jung, D R Littman
Mar 30, 2001·The Journal of Biological Chemistry·G H FanA Richmond
Jun 8, 2001·Annual Review of Biochemistry·S G Rhee
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·M J BerridgeM D Bootman
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·A E WestM E Greenberg
Apr 16, 2003·Molecular Pharmacology·Yoe-Sik BaeSung Ho Ryu
Jul 3, 2003·Nature Reviews. Molecular Cell Biology·Michael J BerridgeH Llewelyn Roderick
Nov 23, 2006·Nature Structural & Molecular Biology·Mark R JezykJohn Sondek
Dec 13, 2006·Circulation Research·Stefan Offermanns
Jan 26, 2007·Nature Reviews. Cancer·Robert T Dorsam, J Silvio Gutkind
Dec 18, 2007·Cell·David E Clapham
Aug 12, 2008·Molecular Cell·Stephanie N HicksJohn Sondek
Jul 11, 2009·The EMBO Journal·Marie-Laure RivesLaurent Prézeau
Aug 12, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mohd W NasserRicardo M Richardson
Sep 15, 2009·European Journal of Immunology·Zhifang ZhangJohn E Shively

❮ Previous
Next ❯

Citations

Feb 14, 2021·International Journal of Molecular Sciences·Manuel GrundmannFrank Eitner
Dec 19, 2020·Molecular Cell·Isaac J Fisher, Angeline M Lyon
Feb 19, 2021·Cell Calcium·Thomas M WilkieSarthak Reddy
Feb 28, 2021·The Journal of Biological Chemistry·Julian PattEvi Kostenis
Apr 17, 2021·ACS Pharmacology & Translational Science·Jonathan G SchlegelChrista E Müller
May 25, 2021·American Journal of Physiology. Renal Physiology·Brian G PollMark A Knepper

❮ Previous
Next ❯

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.