Delineation of the functional properties exhibited by the Zinc-Activated Channel (ZAC) and its high-frequency Thr128Ala variant (rs2257020) in Xenopus oocytes.

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Nawid MadjrohAnders A Jensen

Abstract

The signalling characteristics of the Zinc-Activated Channel (ZAC), a member of the Cys-loop receptor (CLR) superfamily, are presently poorly elucidated. The ZACN polymorphism c.454G>A encoding for the Thr128Ala variation in ZAC is found in extremely high allele frequencies across ethnicities. In this, the first study of ZAC in Xenopus oocytes by TEVC electrophysiology, ZACThr128 and ZACAla128 exhibited largely comparable pharmacological and signalling characteristics, but interestingly the Zn2+- and H+-evoked current amplitudes in ZACAla128-oocytes were dramatically smaller than those in ZACThr128-oocytes. While the variation thus appeared to impact cell surface expression and/or channel properties of ZAC, the similar expression properties exhibited by ZACThr128 and ZACAla128 in transfected mammalian cells indicated that their distinct functionalities could arise from the latter. In co-expression experiments, wild-type and variant ZAC subunits assembled efficiently into "heteromeric" complexes in HEK293 cells, while the concomitant presence of ZACAla128 in ZACThr128:ZACAla128-oocytes did not exert a dominant negative effect on agonist-evoked current amplitudes compared to those in ZACThr128-oocytes. Finally, the structural det...Continue Reading

References

Oct 1, 1980·The Journal of Physiology·F J Sigworth
May 1, 1994·Pflügers Archiv : European journal of physiology·M ChahineR Horn
Oct 17, 2002·The Journal of Biological Chemistry·Paul A DaviesEwen F Kirkness
May 17, 2003·The Journal of Biological Chemistry·Gary W BoydChristopher N Connolly
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 9, 2005·Biochemical and Biophysical Research Communications·Takeshi HoutaniTetsuo Sugimoto
Jun 3, 2006·Methods in Molecular Biology·Steven David BuckinghamDavid Barry Sattelle
May 15, 2007·Pharmacogenetics and Genomics·Karen KrzywkowskiHans Bräuner-Osborne
Jan 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Karen KrzywkowskiAnders A Jensen
Sep 2, 2009·Nature Reviews. Drug Discovery·Antoine TalyJean-Pierre Changeux
Jul 14, 2010·Pharmacology & Therapeutics·Jutta WalstabBeate Niesler
Feb 1, 2011·Expert Opinion on Drug Discovery·Trine KvistHans Bräuner-Osborne
Aug 15, 2014·Nature·Ghérici HassaineHugues Nury
Apr 22, 2015·Nature Communications·Marc GielenTrevor G Smart
May 8, 2015·Nature Protocols·Lawrence A KelleyMichael J E Sternberg
Feb 14, 2016·Biochemical Pharmacology·Sarah M TrattnigPaul A Davies
Feb 16, 2016·Neuron·Shenyan GuDavid S Bredt
Oct 21, 2016·Nature·Claudio L Morales-PerezRyan E Hibbs
Oct 21, 2016·Human Mutation·Jacopo CelliBeate Niesler
May 23, 2017·Advances in Pharmacology·Han Chow Chua, Mary Chebib
May 23, 2017·Advances in Pharmacology·Joseph W LynchArgel Estrada-Mondragon
Jun 16, 2018·Trends in Pharmacological Sciences·Elif EnginUwe Rudolph
Nov 8, 2018·Nature·Lucie PolovinkinHugues Nury
Jan 4, 2019·Nature·Duncan LavertyA Radu Aricescu
Mar 3, 2020·Medicinal Research Reviews·Radomir JuzaJan Korabecny
Apr 10, 2020·Neuropharmacology·Anant GharpureRyan E Hibbs
May 22, 2020·Neurobiology of Stress·Delia BelelliJeremy J Lambert
Feb 5, 2021·The Journal of Biological Chemistry·Georgina KontouJoshua L Smalley

❮ 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.