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Am J Physiol Cell Physiol
2020 Aug 01;3192:C359-C370. doi: 10.1152/ajpcell.00128.2020.
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pH dependence of the Slc4a11-mediated H+ conductance is influenced by intracellular lysine residues and modified by disease-linked mutations.
Quade BN
,
Marshall A
,
Parker MD
.
???displayArticle.abstract??? SLC4A11 is the only member of the SLC4 family that transports protons rather than bicarbonate. SLC4A11 is expressed in corneal endothelial cells, and its mutation causes corneal endothelial dystrophy, although the mechanism of pathogenesis is unknown. We previously demonstrated that the magnitude of the H+ conductance (Gm) mediated by SLC4A11 is increased by rises in intracellular as well as extracellular pH (pHi and pHe). To better understand this feature and whether it is altered in disease, we studied the pH dependence of wild-type and mutant mouse Slc4a11 expressed in Xenopus oocytes. Using voltage-clamp circuitry in conjunction with a H+-selective microelectrode and a microinjector loaded with NaHCO3, we caused incremental rises in oocyte pHi and measured the effect on Gm. We find that the rise of Gm has a steeper pHi dependence at pHe =8.50 than at pHe =7.50. Data gathered at pHe =8.50 can be fit to the Hill equation enabling the calculation of a pK value that reports pHi dependence. We find that mutation of lysine residues that are close to the first transmembrane span (TM1) causes an alkaline shift in pK. Furthermore, two corneal-dystrophy-causing mutations close to the extracellular end of TM1, E399K and T401K (E368K and T370K in mouse), cause an acidic shift in pK, while a third mutation in the fourth intracellular loop, R804H (R774H in mouse), causes an alkaline shift in pK. This is the first description of determinants of SLC4A11 pH dependence and the first indication that a shift in pH dependence could modify disease expressivity in some cases of corneal dystrophy.
Alka,
Ophthalmic Nonsteroidal Anti-Inflammatory Drugs as a Therapy for Corneal Dystrophies Caused by SLC4A11 Mutation.
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Alka,
Ophthalmic Nonsteroidal Anti-Inflammatory Drugs as a Therapy for Corneal Dystrophies Caused by SLC4A11 Mutation.
2018,
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Alka,
Molecular phenotype of SLC4A11 missense mutants: Setting the stage for personalized medicine in corneal dystrophies.
2018,
Pubmed
Bonanno,
Molecular mechanisms underlying the corneal endothelial pump.
2012,
Pubmed
DeCoursey,
Voltage and pH sensing by the voltage-gated proton channel, HV1.
2018,
Pubmed
Decoursey,
Voltage-gated proton channels.
2012,
Pubmed
Desir,
Borate transporter SLC4A11 mutations cause both Harboyan syndrome and non-syndromic corneal endothelial dystrophy.
2007,
Pubmed
Fakler,
Identification of a titratable lysine residue that determines sensitivity of kidney potassium channels (ROMK) to intracellular pH.
1996,
Pubmed
,
Xenbase
Gröger,
SLC4A11 prevents osmotic imbalance leading to corneal endothelial dystrophy, deafness, and polyuria.
2010,
Pubmed
Han,
Mice with a targeted disruption of Slc4a11 model the progressive corneal changes of congenital hereditary endothelial dystrophy.
2013,
Pubmed
Jalimarada,
Ion transport function of SLC4A11 in corneal endothelium.
2013,
Pubmed
Kanki,
The N-terminal region of the transmembrane domain of human erythrocyte band 3. Residues critical for membrane insertion and transport activity.
2003,
Pubmed
,
Xenbase
Kao,
SLC4A11 function: evidence for H+(OH-) and NH3-H+ transport.
2020,
Pubmed
Kao,
Human SLC4A11-C functions as a DIDS-stimulatable H⁺(OH⁻) permeation pathway: partial correction of R109H mutant transport.
2015,
Pubmed
Kurschat,
Alkaline-shifted pHo sensitivity of AE2c1-mediated anion exchange reveals novel regulatory determinants in the AE2 N-terminal cytoplasmic domain.
2006,
Pubmed
,
Xenbase
Lee,
Monitoring ion activities in and around cells using ion-selective liquid-membrane microelectrodes.
2013,
Pubmed
Li,
R125H, W240S, C386R, and V507I SLC4A11 mutations associated with corneal endothelial dystrophy affect the transporter function but not trafficking in PS120 cells.
2019,
Pubmed
Loganathan,
Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies.
2016,
Pubmed
,
Xenbase
Lopez,
Slc4a11 gene disruption in mice: cellular targets of sensorineuronal abnormalities.
2009,
Pubmed
Malhotra,
Defective cell adhesion function of solute transporter, SLC4A11, in endothelial corneal dystrophies.
2020,
Pubmed
Myers,
Mouse Slc4a11 expressed in Xenopus oocytes is an ideally selective H+/OH- conductance pathway that is stimulated by rises in intracellular and extracellular pH.
2016,
Pubmed
,
Xenbase
Nanda,
REVIEW: Current understanding of the pathogenesis of Fuchs' endothelial corneal dystrophy.
2019,
Pubmed
Nehrke,
H(OH), H(OH), H(OH): a holiday perspective. Focus on "Mouse Slc4a11 expressed in Xenopus oocytes is an ideally selective H+/OH- conductance pathway that is stimulated by rises in intracellular and extracellular pH".
2016,
Pubmed
,
Xenbase
Neubig,
International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology.
2003,
Pubmed
Ogando,
SLC4A11 is an EIPA-sensitive Na(+) permeable pHi regulator.
2013,
Pubmed
Park,
NaBC1 is a ubiquitous electrogenic Na+ -coupled borate transporter essential for cellular boron homeostasis and cell growth and proliferation.
2004,
Pubmed
,
Xenbase
Parker,
The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters.
2013,
Pubmed
Stewart,
Regulation of AE2 anion exchanger by intracellular pH: critical regions of the NH(2)-terminal cytoplasmic domain.
2001,
Pubmed
,
Xenbase
Vilas,
Transmembrane water-flux through SLC4A11: a route defective in genetic corneal diseases.
2013,
Pubmed
,
Xenbase
Vithana,
SLC4A11 mutations in Fuchs endothelial corneal dystrophy.
2008,
Pubmed
Vithana,
Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2).
2006,
Pubmed
Weiss,
IC3D classification of corneal dystrophies--edition 2.
2015,
Pubmed
Weiss,
The Hill equation revisited: uses and misuses.
1997,
Pubmed
Zhang,
The cytoplasmic and transmembrane domains of AE2 both contribute to regulation of anion exchange by pH.
1996,
Pubmed
,
Xenbase
Zhang,
Human SLC4A11 Is a Novel NH3/H+ Co-transporter.
2015,
Pubmed
