Activity of Adenylyl Cyclase Type 6 Is Suppressed by Direct Binding of the Cytoskeletal Protein 4.1G

Molecular Pharmacology
Masaki SaitoJun Sukegawa

Abstract

The G protein-coupled receptor (GPCR) signaling pathways mediated by trimeric G proteins have been extensively elucidated, but their associated regulatory mechanisms remain unclear. Parathyroid hormone (PTH)/PTH-related protein receptor (PTHR) is a GPCR coupled with Gs and Gq Gs activates adenylyl cyclases (ACs), which produces cAMP to regulate various cell fates. We previously showed that cell surface expression of PTHR was increased by its direct interaction with a subcortical cytoskeletal protein, 4.1G, whereas PTHR-mediated Gs/AC/cAMP signaling was suppressed by 4.1G through an unknown mechanism in human embryonic kidney (HEK)293 cells. In the present study, we found that AC type 6 (AC6), one of the major ACs activated downstream of PTHR, interacts with 4.1G in HEK293 cells, and the N-terminus of AC6 (AC6-N) directly and selectively binds to the 4.1/ezrin/radixin/moesin (FERM) domain of 4.1G (4.1G-FERM) in vitro. AC6-N was distributed at the plasma membrane, which was disturbed by knockdown of 4.1G. An AC6-N mutant, AC6-N-3A, in which three consecutive arginine residues are mutated to alanine residues, altered both binding to 4.1G-FERM and its plasma membrane distribution in vivo. Further, we overexpressed AC6-N to competit...Continue Reading

References

Jan 13, 1995·The Journal of Biological Chemistry·P B WedegaertnerH R Bourne
Aug 29, 1997·The Journal of Biological Chemistry·R K SunaharaA G Gilman
May 26, 1998·The EMBO Journal·M L Dell'AcquaJ D Scott
Aug 16, 2002·Molecular Pharmacology·Alicia V BindaRobert Levenson
Oct 26, 2002·Science·Stephen J PerryRobert J Lefkowitz
Mar 13, 2003·Kidney International·Mohamed RamezPhilippe Gascard
Oct 25, 2003·Biochemical and Biophysical Research Communications·Maki SugaiJun Sukegawa
Jul 21, 2005·The Biochemical Journal·Masaki SaitoNorimichi Nakahata
Jul 7, 2007·Physiological Reviews·Debbie Willoughby, Dermot M F Cooper
Nov 15, 2008·Cellular Signalling·Muthusamy ThangavelRennolds S Ostrom
Aug 25, 2009·Nature Chemical Biology·Sébastien FerrandonJean-Pierre Vilardaga
Mar 30, 2011·Nature Chemical Biology·Timothy N FeinsteinJean-Pierre Vilardaga
Jul 21, 2011·The Journal of Biological Chemistry·Ilse Delint-RamirezDermot M F Cooper
Sep 10, 2011·International Journal of Cell Biology·Wataru NunomuraYuichi Takakuwa
Apr 23, 2014·PloS One·Shailesh R AgarwalRobert D Harvey
May 24, 2014·Journal of the American Society of Nephrology : JASN·Robert A FentonTimo Rieg
Aug 8, 2014·The Biochemical Journal·Dermot M F Cooper, Valentina G Tabbasum
May 30, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alexander HeinickFrank U Müller
Jul 25, 2015·Molecular Pharmacology·Cameron S BrandCarmen W Dessauer
Apr 14, 2016·Biochemical Society Transactions·Andrew M Ellisdon, Michelle L Halls

❮ 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.