Varying selection pressure for a Na+ sensing site in epithelial Na+ channel subunits reflect divergent roles in Na+ homeostasis DOI Creative Commons
Xue‐Ping Wang, Priyanka Srinivasan, Mustapha El Hamdaoui

и другие.

Molecular Biology and Evolution, Год журнала: 2024, Номер 41(8)

Опубликована: Авг. 1, 2024

The epithelial Na+ channel (ENaC) emerged early in vertebrates and has played a role fluid homeostasis throughout vertebrate evolution. We previously showed that proteolytic activation of the evolved at water-to-land transition vertebrates. Sensitivity to extracellular Na+, known as self-inhibition, reduces ENaC function when concentrations are high is distinctive feature channel. A fourth subunit, δ, jawed fishes from an α subunit gene duplication. Here, we analyzed 849 δ sequences found key Asp postulated binding site was nearly always present but frequently lost (e.g. human). Analysis evolution codon substitution rates provide evidence ancestral had purifying selection for relaxed after its divergence coinciding with loss expression renal tissues. also show proposed bona fide by conferring novel channels comprising human subunits. Together, our findings self-inhibition improves fitness through

Язык: Английский

Role of Actin Dynamics in the Control of Proteolytically Induced ENaC-Like Channel Activity in Human Leukemia Cells DOI
Daria V. Lysikova, Valeria Y. Vasileva, Olga Tsaplina

и другие.

Cell and Tissue Biology, Год журнала: 2025, Номер 19(1), С. 48 - 54

Опубликована: Янв. 20, 2025

Язык: Английский

Процитировано

0
Automated patch-clamp recordings for detecting activators and inhibitors of the epithelial sodium channel (ENaC) DOI Creative Commons
Florian Sure, Markus Rapedius,

Alexei Diakov

и другие.

Pflügers Archiv - European Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Май 8, 2025

Abstract The epithelial sodium channel (ENaC) is crucial for absorption in several tissues including lung and kidney. Its involvement various renal pulmonary disorders makes ENaC a potential drug target. High-throughput screening using the automated patch-clamp (APC) technique appears to be promising approach discover novel modulators with (patho-)physiological therapeutic implications. aim of this methodological study was establish APC measurements ENaC-mediated currents. First, we confirmed functional expression HEK293 cell line stably transfected human αβγ-ENaC conventional manual whole-cell recordings. For measurements, standard enzymatic cell-detachment procedure used prepare single suspensions. This resulted high success rate recordings amiloride inhibitable Using γ-inhibitory peptide small molecule activator S3969, demonstrate that could reveal inhibitory as well stimulatory effects on ENaC. Interestingly, protocol partial proteolytic activation. portion proteolytically activated channels reduced by prolonged incubation suspended cells culture medium. recovery enhanced relative effect chymotrypsin, prototypical serine protease known cause Thus, may particularly useful identifying activators mimicking In conclusion, have established high-throughput method identification inhibitors APC.

Язык: Английский

Процитировано

0
Influence of proteolytic cleavage of ENaC’s γ subunit upon Na+ and K+ handling DOI
Evan C. Ray, Andrew J. Nickerson, Shaohu Sheng

и другие.

AJP Renal Physiology, Год журнала: 2024, Номер 326(6), С. F1066 - F1077

Опубликована: Апрель 18, 2024

The epithelial Na

Язык: Английский

Процитировано

3
Loss of the alpha subunit distal furin cleavage site blunts ENaC activation following Na+ restriction DOI Creative Commons
Andrew J. Nickerson, Shaohu Sheng,

Natalie A. Cox

и другие.

The Journal of Physiology, Год журнала: 2024, Номер 602(17), С. 4309 - 4326

Опубликована: Авг. 28, 2024

Abstract Epithelial Na + channels (ENaCs) are activated by proteolysis of the α and γ subunits at specific sites flanking embedded inhibitory tracts. To examine role subunit in channel activation vivo , we generated mice lacking distal furin cleavage site (α F2M mice). On a normal control diet, no differences ENaC protein abundance kidney or colon were noted between wild‐type (WT) mice. Patch‐clamp analyses revealed similar levels activity tubules, while physiologically relevant blood chemistry aldosterone detected. Male did exhibit diminished colon, as measured amiloride‐sensitive short‐circuit current ( I SC ). Following dietary restriction, WT had natriuretic colonic responses to amiloride. However, single‐channel was significantly lower tubules from ‐restricted compared with littermates. expression also enhanced vs . mice, association higher levels. These data provide evidence that disrupting impairs requiring compensation response restriction. image Key points The epithelial (ENaC) is proteolytic vitro but key questions regarding terms whole‐animal physiology remain be addressed. We studied importance this mechanism generating mouse model genetic disruption ENaC's found not phenotype under conditions, have impaired (channel open probability) during salt function organ level preserved salt‐restricted associated increased subunits, suggesting required maintain homeostasis. results first regulator

Язык: Английский

Процитировано

1
Going with the flow: New insights regarding flow induced K+ secretion in the distal nephron DOI Creative Commons
Samia Lasaad, Andrew J. Nickerson, Gilles Crambert

и другие.

Physiological Reports, Год журнала: 2024, Номер 12(20)

Опубликована: Окт. 1, 2024

Abstract K + secretion in the distal nephron has a critical role homeostasis and is primary route by which lost from body. Renal enhanced increases dietary intake tubular flow rate nephron. This review addresses new important insights regarding mechanisms underlying flow‐induced (FIKS). While basal mediated renal outer medullary (ROMK) channels principal cells (PCs), FIKS large conductance, Ca 2+ /stretch activated (BK) intercalated (ICs), distinct cell type. BK channel activation requires an increase intracellular concentration ([Ca ] i ), both PCs ICs exhibit [Ca response to fluid rate, associated with diameter. PIEZO1, mechanosensitive, nonselective cation channel, expressed basolateral membranes of ICs, where it functions as mechanosensor. The loss transients channel‐mediated microperfused collecting ducts isolated mice IC‐specific deletion Piezo1 CCD underscores importance PIEZO1 regulation transport.

Язык: Английский

Процитировано

1
Varying selection pressure for a Na+sensing site in epithelial Na+channel subunits reflect divergent roles in Na+homeostasis DOI Creative Commons
Xue‐Ping Wang, Priyanka Srinivasan, Mustapha El Hamdaoui

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 21, 2024

Abstract The epithelial Na + channel (ENaC) emerged early in vertebrates and has played a role fluid homeostasis throughout vertebrate evolution. We previously showed that proteolytic activation of the evolved at water to land transition vertebrates. Sensitivity extracellular , known as self-inhibition, reduces ENaC function when concentrations are high is distinctive feature channel. A fourth subunit, δ, jawed fishes from an α subunit gene duplication. Here, we analyzed 846 δ sequences found key Asp postulated binding site was nearly always present but frequently lost (e.g., human). Analysis evolution codon substitution rates provide evidence ancestral had purifying selection for relaxed after its divergence coinciding with loss expression renal tissues. also proposed bona fide by conferring novel channels comprising human subunits. Together, our findings self-inhibition improves fitness through

Язык: Английский

Процитировано

0
Varying selection pressure for a Na+ sensing site in epithelial Na+ channel subunits reflect divergent roles in Na+ homeostasis DOI Creative Commons
Xue‐Ping Wang, Priyanka Srinivasan, Mustapha El Hamdaoui

и другие.

Molecular Biology and Evolution, Год журнала: 2024, Номер 41(8)

Опубликована: Авг. 1, 2024

The epithelial Na+ channel (ENaC) emerged early in vertebrates and has played a role fluid homeostasis throughout vertebrate evolution. We previously showed that proteolytic activation of the evolved at water-to-land transition vertebrates. Sensitivity to extracellular Na+, known as self-inhibition, reduces ENaC function when concentrations are high is distinctive feature channel. A fourth subunit, δ, jawed fishes from an α subunit gene duplication. Here, we analyzed 849 δ sequences found key Asp postulated binding site was nearly always present but frequently lost (e.g. human). Analysis evolution codon substitution rates provide evidence ancestral had purifying selection for relaxed after its divergence coinciding with loss expression renal tissues. also show proposed bona fide by conferring novel channels comprising human subunits. Together, our findings self-inhibition improves fitness through

Язык: Английский

Процитировано

0