Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels

Proceedings of the National Academy of Sciences of the United States of America
Christian J PetersLily Y Jan

Abstract

TMEM16A (transmembrane protein 16) (Anoctamin-1) forms a calcium-activated chloride channel (CaCC) that regulates a broad array of physiological properties in response to changes in intracellular calcium concentration. Although known to conduct anions according to the Eisenman type I selectivity sequence, the structural determinants of TMEM16A anion selectivity are not well-understood. Reasoning that the positive charges on basic residues are likely contributors to anion selectivity, we performed whole-cell recordings of mutants with alanine substitution for basic residues within the putative pore region and identified four residues on four different putative transmembrane segments that significantly increased the permeability of the larger halides and thiocyanate relative to that of chloride. Because TMEM16A permeation properties are known to shift with changes in intracellular calcium concentration, we further examined the calcium dependence of anion selectivity. We found that WT TMEM16A but not mutants with alanine substitution at those four basic residues exhibited a clear decline in the preference for larger anions as intracellular calcium was increased. Having implicated these residues as contributing to the TMEM16A pore,...Continue Reading

References

Mar 1, 1989·Pflügers Archiv : European journal of physiology·M Lupu-MeiriY Oron
Jan 14, 1999·The American Journal of Physiology·A Kuruma, H C Hartzell
Dec 30, 1999·The Journal of General Physiology·A Kuruma, H C Hartzell
Jun 25, 2004·The Journal of Membrane Biology·P Perez-CornejoJ Arreola
Dec 18, 2007·Molecular Pharmacology·Ricardo De La FuenteA S Verkman
May 31, 2008·Contributions to Microbiology·Balázs Rada, Thomas L Leto
Sep 23, 2008·Cell·Björn Christian SchroederLily Yeh Jan
May 29, 2009·Pflügers Archiv : European journal of physiology·Simone PifferiAnna Menini
Aug 15, 2009·The Journal of Biological Chemistry·Jiraporn OusingsawatKarl Kunzelmann
Oct 13, 2009·The Journal of Biological Chemistry·Loretta FerreraLuis J V Galietta
Dec 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·Fen HuangLily Yeh Jan
Feb 24, 2010·The Journal of Biological Chemistry·Victor G RomanenkoJames E Melvin
Jun 29, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wan NamkungA S Verkman
Aug 6, 2010·American Journal of Physiology. Cell Physiology·Alison J DavisNormand Leblanc
Nov 25, 2011·American Journal of Physiology. Renal Physiology·Maria SanchoDomingo Triguero
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Fen HuangJason R Rock
Dec 20, 2013·Pflügers Archiv : European journal of physiology·J P ReyesA Martínez-Torres
Jan 15, 2014·The Journal of General Physiology·Kuai YuH Criss Hartzell
Mar 20, 2014·Channels·Eamonn BradleyGerard P Sergeant
May 28, 2014·The Journal of General Physiology·Giulia BettoAnna Menini
Oct 10, 2014·American Journal of Physiology. Cell Physiology·L TwyffelsV Kruys
Nov 11, 2014·Nature·Janine D BrunnerRaimund Dutzler
Dec 23, 2014·Channels·Kenton M SandersNormand Leblanc

❮ Previous
Next ❯

Citations

Jan 8, 2016·Pflügers Archiv : European journal of physiology·Jarred M Whitlock, H Criss Hartzell
Jan 27, 2016·Pflügers Archiv : European journal of physiology·Uhtaek Oh, Jooyoung Jung
Jan 6, 2016·The Journal of Physiology·Silvia Cruz-RangelJorge Arreola
Dec 15, 2015·Acta Pharmacologica Sinica·Hai-bo YuXiao-liang Wang
Nov 28, 2015·Mediators of Inflammation·Monica Sala-RabanalTom J Brett
Sep 30, 2016·Journal of Cellular Physiology·Ke MaQinghuan Xiao
Nov 2, 2016·The Journal of General Physiology·Novandy K LimRaimund Dutzler
Nov 2, 2016·The Journal of General Physiology·H Criss Hartzell, Jarred M Whitlock
Jan 26, 2017·Journal of Cellular Physiology·Mohammad Amin Kamaleddin
Jun 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Sayuri GyobuShigekazu Nagata
Dec 14, 2017·Nature·Shangyu DangLily Yeh Jan
Jun 7, 2018·American Journal of Physiology. Cell Physiology·Xu CaoBret A Hughes
Nov 22, 2019·Journal of Computational Chemistry·George KhelashviliHarel Weinstein
Apr 23, 2020·Assay and Drug Development Technologies·Kathryn A HenckelsJonathan E Phillips
Jun 20, 2018·The Journal of General Physiology·Maria E FalzoneAlessio Accardi
Aug 16, 2018·Nature Communications·Byoung-Cheol LeeAlessio Accardi
Nov 23, 2016·Proceedings of the National Academy of Sciences of the United States of America·Neville P Bethel, Michael Grabe
May 12, 2018·International Journal of Molecular Sciences·Trey S RottgenVazhaikkurichi M Rajendran
Mar 25, 2019·International Journal of Molecular Sciences·Marcin MagaczWirginia Krzyściak
Dec 6, 2018·Journal of Cellular Physiology·Qiushuang JiHailong An
Sep 8, 2018·Nature Structural & Molecular Biology·Mingfeng ZhangLei Chen
Apr 8, 2020·Computational and Structural Biotechnology Journal·Sai ShiHailong An
Feb 28, 2021·Communications Biology·Zhiguang Jia, Jianhan Chen
Mar 21, 2021·Journal of Molecular Biology·Valeria KalienkovaCristina Paulino
May 6, 2021·Physiological Reviews·Ole H PetersenShuang Peng
Feb 18, 2017·Analytical Chemistry·Marie FuestShaurya Prakash
Aug 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ria L DinsdalePaolo Tammaro
Nov 15, 2021·The FEBS Journal·Anna BoccaccioJoachim Scholz-Starke

❮ 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.