Large transient capacitive currents in wild-type lysosomal Cl-/H+ antiporter ClC-7 and residual transport activity in the proton glutamate mutant E312A.

The Journal of General Physiology
Michael Pusch, Giovanni Zifarelli

Abstract

ClC-7 is a lysosomal 2 Cl-/1 H+ antiporter of the CLC protein family, which comprises Cl- channels and other Cl-/H+ antiporters. Mutations in ClC-7 and its associated β subunit Ostm1 lead to osteopetrosis and lysosomal storage disease in humans and mice. Previous studies on other mammalian CLC transporters showed that mutations of a conserved, intracellularly located glutamate residue, the so-called proton glutamate, abolish steady-state transport activity but increase transient capacitive currents associated with partial reactions of the transport cycle. In contrast, we observed large, transient capacitive currents for the wild-type ClC-7, which depend on external pH and internal, but not external, Cl-. Very similar transient currents were observed for the E312A mutant of the proton glutamate. Interestingly, and unlike in other mammalian CLC transporters investigated so far, the E312A mutation strongly reduces, but does not abolish, stationary transport currents, potentially explaining the intermediate phenotype observed in the E312A mouse line.

References

Dec 1, 1982·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·C Miller
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·W GüntherT J Jentsch
Mar 22, 2003·Science·Raimund DutzlerRoderick MacKinnon
Aug 9, 2003·The Journal of Biological Chemistry·Deanne H HryciwWilliam B Guggino
Aug 13, 2003·The Journal of General Physiology·Alessio Accardi, Michael Pusch
Jan 14, 2004·The Journal of General Physiology·Alessio AccardiChristopher Miller
Feb 12, 2005·The EMBO Journal·Dagmar KasperThomas J Jentsch
Jul 22, 2005·Nature·Alessandra Picollo, Michael Pusch
Dec 1, 2005·The Journal of General Physiology·Alessio AccardiChristopher Miller
Mar 29, 2007·The Journal of General Physiology·Michael WaldenChristopher Miller
Aug 31, 2007·Reviews of Physiology, Biochemistry and Pharmacology·G Zifarelli, M Pusch
Dec 8, 2007·The Journal of Biological Chemistry·Anselm A ZdebikMichael Pusch
Mar 21, 2008·Nature Reviews. Molecular Cell Biology·Francisco Bezanilla
Jan 14, 2009·The Journal of General Physiology·Hyun-Ho Lim, Christopher Miller
May 15, 2010·The Journal of Biological Chemistry·Ioana NeagoeThomas J Jentsch
May 27, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andrew J Smith, Jonathan D Lippiat
Sep 8, 2010·The Journal of Biological Chemistry·Tobias Stauber, Thomas J Jentsch
Jan 24, 2012·The Journal of Biological Chemistry·Matthias Grieschat, Alexi K Alekov
Jul 25, 2012·Biophysical Journal·Giovanni ZifarelliMichael Pusch
Feb 8, 2013·Scientific Reports·Ilaria ZanardiMichael Pusch
Mar 21, 2013·ACS Chemical Neuroscience·Raul E GuzmanAlexi K Alekov
Oct 9, 2013·The Journal of Physiology·Silvia De StefanoGiovanni Zifarelli
Dec 22, 2016·Nature·Eunyong ParkRoderick MacKinnon
May 29, 2018·ELife·Eunyong Park, Roderick MacKinnon
May 31, 2018·Physiological Reviews·Thomas J Jentsch, Michael Pusch
Apr 26, 2019·PLoS Biology·Kaituo WangPontus Gourdon
Aug 28, 2020·Science Advances·Sensen ZhangMaojun Yang

❮ Previous
Next ❯

Citations

Mar 13, 2021·Frontiers in Cell and Developmental Biology·Shroddha BoseTobias Stauber
Aug 28, 2021·International Journal of Molecular Sciences·Loretta FerreraMichael Pusch

❮ Previous
Next ❯

Software Mentioned

Systat
Ana
ORIGIN
SigmaPlot
Pymol
GePulse

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.

Related Papers

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
L WartoschThomas J Jentsch
Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Eleonora Di ZanniAlessandra Picollo
© 2021 Meta ULC. All rights reserved