scholarly journals Activation by cleavage of the epithelial Na+ channel α and γ subunits independently coevolved with the vertebrate terrestrial migration

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Xue-Ping Wang ◽  
Deidra M Balchak ◽  
Clayton Gentilcore ◽  
Nathan L Clark ◽  
Ossama B Kashlan
Keyword(s):  
Gas Exchange ◽  
Extracellular Fluid ◽  
Na Channel ◽  
Fluid Homeostasis ◽  
Terrestrial Habitats ◽  
Protease Activation ◽  
Epithelial Na Channel ◽  
Alveolar Gas Exchange

Vertebrates evolved mechanisms for sodium conservation and gas exchange in conjunction with migration from aquatic to terrestrial habitats. Epithelial Na+ channel (ENaC) function is critical to systems responsible for extracellular fluid homeostasis and gas exchange. ENaC is activated by cleavage at multiple specific extracellular polybasic sites, releasing inhibitory tracts from the channel’s α and γ subunits. We found that proximal and distal polybasic tracts in ENaC subunits coevolved, consistent with the dual cleavage requirement for activation observed in mammals. Polybasic tract pairs evolved with the terrestrial migration and the appearance of lungs, coincident with the ENaC activator aldosterone, and appeared independently in the a and g subunits. In summary, sites within ENaC for protease activation developed in vertebrates when renal Na+ conservation and alveolar gas exchange was required for terrestrial survival.

scholarly journals Activation by Cleavage of the Epithelial Na+ Channel α and γ Subunits Independently Coevolved with the Vertebrate Terrestrial Migration

2020 ◽  
Author(s):  
Xue-Ping Wang ◽  
Deidra M. Balchak ◽  
Clayton Gentilcore ◽  
Nathan L. Clark ◽  
Ossama B. Kashlan
Keyword(s):  
Gas Exchange ◽  
Extracellular Fluid ◽  
Na Channel ◽  
Fluid Homeostasis ◽  
Terrestrial Habitats ◽  
Protease Activation ◽  
Epithelial Na Channel ◽  
Alveolar Gas Exchange

AbstractVertebrates evolved mechanisms for sodium conservation and gas exchange in conjunction with migration from aquatic to terrestrial habitats. Epithelial Na+ channel (ENaC) function is critical to systems responsible for extracellular fluid homeostasis and gas exchange. ENaC is activated by cleavage at multiple specific extracellular polybasic sites, releasing inhibitory tracts from the channel’s α and γ subunits. We found that proximal and distal polybasic tracts in ENaC subunits coevolved, consistent with the dual cleavage requirement for activation observed in mammals. Polybasic tract pairs evolved with the terrestrial migration and the appearance of lungs, coincident with the ENaC activator aldosterone, and appeared independently in the αand γ subunits. In summary, sites within ENaC for protease activation developed in vertebrates when renal Na+ conservation and alveolar gas exchange was required for terrestrial survival.

scholarly journals Differential Effects of Protein Kinase C on the Levels of Epithelial Na+Channel Subunit Proteins

2000 ◽  
Vol 275 (33) ◽  
pp. 25760-25765 ◽  
Author(s):  
James D. Stockand ◽  
Hui-Fang Bao ◽  
Julie Schenck ◽  
Bela Malik ◽  
Pam Middleton ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Na Channel ◽  
Differential Effects ◽  
Kinase C ◽  
Epithelial Na Channel

scholarly journals CRISPR/Cas9 Mediated Knock Down of δ-ENaC Blunted the TNF-Induced Activation of ENaC in A549 Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1858
Author(s):  
Waheed Shabbir ◽  
Nermina Topcagic ◽  
Mohammed Aufy ◽  
Murat Oz
Keyword(s):  
A549 Cells ◽  
Na Channel ◽  
Na Current ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Knock Down ◽  
Whole Cell Patch Clamp ◽  
Glycosylation Sites ◽  
Epithelial Na Channel

Tumor necrosis factor (TNF) is known to activate the epithelial Na+ channel (ENaC) in A549 cells. A549 cells are widely used model for ENaC research. The role of δ-ENaC subunit in TNF-induced activation has not been studied. In this study we hypothesized that δ-ENaC plays a major role in TNF-induced activation of ENaC channel in A549 cells which are widely used model for ENaC research. We used CRISPR/Cas 9 approach to knock down (KD) the δ-ENaC in A549 cells. Western blot and immunofluorescence assays were performed to analyze efficacy of δ-ENaC protein KD. Whole-cell patch clamp technique was used to analyze the TNF-induced activation of ENaC. Overexpression of wild type δ-ENaC in the δ-ENaC KD of A549 cells restored the TNF-induced activation of whole-cell Na+ current. Neither N-linked glycosylation sites nor carboxyl terminus domain of δ-ENaC was necessary for the TNF-induced activation of whole-cell Na+ current in δ-ENaC KD of A549 cells. Our data demonstrated that in A549 cells the δ-ENaC plays a major role in TNF-induced activation of ENaC.

scholarly journals Acute effects of aldosterone on the epithelial Na channel in rat kidney

2015 ◽  
Vol 308 (6) ◽  
pp. F572-F578 ◽  
Author(s):  
Gustavo Frindt ◽  
Lawrence G. Palmer
Keyword(s):  
Rat Kidney ◽  
Surface Protein ◽  
Early Response ◽  
Surface Expression ◽  
Na Channel ◽  
Channel Activity ◽  
Acute Effects ◽  
Chronic Stimulation ◽  
Epithelial Na Channels ◽  
Epithelial Na Channel

The acute effects of aldosterone administration on epithelial Na channels (ENaC) in rat kidney were examined using electrophysiology and immunodetection. Animals received a single injection of aldosterone (20 μg/kg body wt), which reduced Na excretion over the next 3 h. Channel activity was assessed in principal cells of cortical collecting ducts as amiloride-sensitive whole cell clamp current ( INa). INa averaged 100 pA/cell, 20–30% of that reported for the same preparation under conditions of chronic stimulation. INa was negligible in control animals that did not receive hormone. The acute physiological response correlated with changes in ENaC processing and trafficking. These effects included increases in the cleaved forms of α-ENaC and γ-ENaC, assessed by Western blot, and increases in the surface expression of β-ENaC and γ-ENaC measured after surface protein biotinylation. These changes were qualitatively and quantitatively similar to those of chronic stimulation. This suggests that altered trafficking to or from the apical membrane is an early response to the hormone and that later increases in channel activity require stimulation of channels residing at the surface.

scholarly journals Maturation of the Epithelial Na+ Channel Involves Proteolytic Processing of the α- and γ-Subunits

2003 ◽  
Vol 278 (39) ◽  
pp. 37073-37082 ◽  
Author(s):  
Rebecca P. Hughey ◽  
Gunhild M. Mueller ◽  
James B. Bruns ◽  
Carol L. Kinlough ◽  
Paul A. Poland ◽  
...  
Keyword(s):  
Proteolytic Processing ◽  
Na Channel ◽  
Epithelial Na Channel

The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel α,β,γ-ENaC

2003 ◽  
Vol 445 (6) ◽  
pp. 693-696 ◽  
Author(s):  
B. Friedrich ◽  
Y. Feng ◽  
P. Cohen ◽  
T. Risler ◽  
A. Vandewalle ◽  
...  
Keyword(s):  
Na Channel ◽  
Threonine Kinases ◽  
Epithelial Na Channel

scholarly journals Na delivery and ENaC mediate flow regulation of collecting duct endothelin-1 production

2012 ◽  
Vol 302 (10) ◽  
pp. F1325-F1330 ◽  
Author(s):  
Meghana M. Pandit ◽  
Kevin A. Strait ◽  
Toshio Matsuda ◽  
Donald E. Kohan
Keyword(s):  
Plasma Membrane ◽  
Collecting Duct ◽  
Extracellular Fluid ◽  
Na Channel ◽  
Endothelin 1 ◽  
Flow Response ◽  
Mrna Content ◽  
Static Conditions ◽  
Biologic System

Collecting duct (CD) endothelin-1 (ET-1) is an important autocrine inhibitor of Na and water transport. CD ET-1 production is stimulated by extracellular fluid volume expansion and tubule fluid flow, suggesting a mechanism coupling CD Na delivery and ET-1 synthesis. A mouse cortical CD cell line, mpkCCDc14, was subjected to static or flow conditions for 2 h at 2 dyn/cm2, followed by determination of ET-1 mRNA content. Flow with 300 mosmol/l NaCl increased ET-1 mRNA to 65% above that observed under static conditions. Increasing perfusate osmolarity to 450 mosmol/l with NaCl or Na acetate increased ET-1 mRNA to ∼184% compared with no flow, which was not observed when osmolarity was increased using mannitol or urea. Reducing Na concentration to 150 mosmol/l while maintaining total osmolarity at 300 mosmol/l with urea or mannitol decreased the flow response. Inhibition of epithelial Na channel (ENaC) with amiloride or benzamil abolished the flow response, suggesting involvement of ENaC in flow-regulated ET-1 synthesis. Aldosterone almost doubled the flow response. Since Ca2+ enhances CD ET-1 production, the involvement of plasma membrane and mitochondrial Na/Ca2+ exchangers (NCX) was assessed. SEA0400 and KB-R7943, plasma membrane NCX inhibitors, did not affect the flow response. However, CGP37157, a mitochondrial NCX inhibitor, abolished the response. In summary, the current study indicates that increased Na delivery, leading to ENaC-mediated Na entry and mitochondrial NCX activity, is involved in flow-stimulated CD ET-1 synthesis. This constitutes the first report of either ENaC or mitochondrial NCX regulation of an autocrine factor in any biologic system.

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