Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2010 Oct 01;28540:30453-62. doi: 10.1074/jbc.M110.151845.
Show Gene links
Show Anatomy links
Cys palmitoylation of the beta subunit modulates gating of the epithelial sodium channel.
Mueller GM
,
Maarouf AB
,
Kinlough CL
,
Sheng N
,
Kashlan OB
,
Okumura S
,
Luthy S
,
Kleyman TR
,
Hughey RP
.
???displayArticle.abstract???
The epithelial Na(+) channel (ENaC) is comprised of three homologous subunits (α, β, and γ) that have a similar topology with two transmembrane domains, a large extracellular region, and cytoplasmic N and C termini. Although ENaC activity is regulated by a number of factors, palmitoylation of its cytoplasmic Cys residues has not been previously described. Fatty acid-exchange chemistry was used to determine whether channel subunits were Cys-palmitoylated. We observed that only the β and γ subunits were modified by Cys palmitoylation. Analyses of ENaCs with mutant β subunits revealed that Cys-43 and Cys-557 were palmitoylated. Xenopus oocytes expressing ENaC with a β C43A,C557A mutant had significantly reduced amiloride-sensitive whole cell currents, enhanced Na(+) self-inhibition, and reduced single channel P(o) when compared with wild-type ENaC, while membrane trafficking and levels of surface expression were unchanged. Computer modeling of cytoplasmic domains indicated that β Cys-43 is in proximity to the first transmembrane α helix, whereas β Cys-557 is within an amphipathic α-helix contiguous with the second transmembrane domain. We propose that β subunit palmitoylation modulates channel gating by facilitating interactions between cytoplasmic domains and the plasma membrane.
Ahn,
Cloning and functional expression of the mouse epithelial sodium channel.
1999, Pubmed,
Xenbase
Ahn,
Cloning and functional expression of the mouse epithelial sodium channel.
1999,
Pubmed
,
Xenbase
Alvarez,
Inhibition of the receptor-mediated endocytosis of diferric transferrin is associated with the covalent modification of the transferrin receptor with palmitic acid.
1990,
Pubmed
Alvarez de la Rosa,
Effects of aldosterone on biosynthesis, traffic, and functional expression of epithelial sodium channels in A6 cells.
2002,
Pubmed
,
Xenbase
Bruns,
Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit.
2007,
Pubmed
,
Xenbase
Bruns,
Multiple epithelial Na+ channel domains participate in subunit assembly.
2003,
Pubmed
,
Xenbase
Butterworth,
The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel.
2007,
Pubmed
Butterworth,
Some assembly required: putting the epithelial sodium channel together.
2008,
Pubmed
Carattino,
Mutations in the pore region modify epithelial sodium channel gating by shear stress.
2005,
Pubmed
,
Xenbase
Carattino,
Arachidonic acid regulates surface expression of epithelial sodium channels.
2003,
Pubmed
,
Xenbase
Carattino,
The epithelial Na+ channel is inhibited by a peptide derived from proteolytic processing of its alpha subunit.
2006,
Pubmed
,
Xenbase
Carattino,
Epithelial sodium channel inhibition by AMP-activated protein kinase in oocytes and polarized renal epithelial cells.
2005,
Pubmed
,
Xenbase
Chen,
A sensory neuron-specific, proton-gated ion channel.
1998,
Pubmed
Crane,
Reversible, temperature-dependent supramolecular assembly of aquaporin-4 orthogonal arrays in live cell membranes.
2009,
Pubmed
Drisdel,
Assays of protein palmitoylation.
2006,
Pubmed
Drisdel,
Labeling and quantifying sites of protein palmitoylation.
2004,
Pubmed
Fang,
GODZ-mediated palmitoylation of GABA(A) receptors is required for normal assembly and function of GABAergic inhibitory synapses.
2006,
Pubmed
Fernández-Hernando,
Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase.
2006,
Pubmed
Gonnord,
Palmitoylation of the P2X7 receptor, an ATP-gated channel, controls its expression and association with lipid rafts.
2009,
Pubmed
Gonzales,
Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.
2009,
Pubmed
Gründer,
A mutation causing pseudohypoaldosteronism type 1 identifies a conserved glycine that is involved in the gating of the epithelial sodium channel.
1997,
Pubmed
,
Xenbase
Gubitosi-Klug,
The human Kv1.1 channel is palmitoylated, modulating voltage sensing: Identification of a palmitoylation consensus sequence.
2005,
Pubmed
Hamm,
Regulation of sodium transport by ENaC in the kidney.
2010,
Pubmed
Harris,
A novel neutrophil elastase inhibitor prevents elastase activation and surface cleavage of the epithelial sodium channel expressed in Xenopus laevis oocytes.
2007,
Pubmed
,
Xenbase
Heneghan,
The Ca2+ channel beta subunit determines whether stimulation of Gq-coupled receptors enhances or inhibits N current.
2009,
Pubmed
Hérincs,
DCC association with lipid rafts is required for netrin-1-mediated axon guidance.
2005,
Pubmed
Hill,
Endogenously expressed epithelial sodium channel is present in lipid rafts in A6 cells.
2002,
Pubmed
Hill,
The epithelial sodium channel (ENaC) traffics to apical membrane in lipid rafts in mouse cortical collecting duct cells.
2007,
Pubmed
,
Xenbase
Hughey,
Epithelial sodium channels are activated by furin-dependent proteolysis.
2004,
Pubmed
,
Xenbase
Hughey,
Distinct pools of epithelial sodium channels are expressed at the plasma membrane.
2004,
Pubmed
,
Xenbase
Hughey,
Maturation of the epithelial Na+ channel involves proteolytic processing of the alpha- and gamma-subunits.
2003,
Pubmed
,
Xenbase
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Jindal,
Posttranslational modification of voltage-dependent potassium channel Kv1.5: COOH-terminal palmitoylation modulates its biological properties.
2008,
Pubmed
Kashlan,
Small heat shock protein alphaA-crystallin regulates epithelial sodium channel expression.
2007,
Pubmed
,
Xenbase
Kellenberger,
Intracellular thiol-mediated modulation of epithelial sodium channel activity.
2005,
Pubmed
,
Xenbase
Kinlough,
Recycling of MUC1 is dependent on its palmitoylation.
2006,
Pubmed
Kleyman,
ENaC at the cutting edge: regulation of epithelial sodium channels by proteases.
2009,
Pubmed
Knight,
Liddle's syndrome mutations increase Na+ transport through dual effects on epithelial Na+ channel surface expression and proteolytic cleavage.
2006,
Pubmed
Lam,
Palmitoylation by the DHHC protein Pfa4 regulates the ER exit of Chs3.
2006,
Pubmed
Lefkowitz,
Transduction of receptor signals by beta-arrestins.
2005,
Pubmed
Linder,
Palmitoylation: policing protein stability and traffic.
2007,
Pubmed
Maarouf,
Novel determinants of epithelial sodium channel gating within extracellular thumb domains.
2009,
Pubmed
,
Xenbase
Malik,
Regulation of epithelial sodium channels by the ubiquitin-proteasome proteolytic pathway.
2006,
Pubmed
May,
Early effect of aldosterone on the rate of synthesis of the epithelial sodium channel alpha subunit in A6 renal cells.
1997,
Pubmed
,
Xenbase
Mueller,
Epithelial sodium channel exit from the endoplasmic reticulum is regulated by a signal within the carboxyl cytoplasmic domain of the alpha subunit.
2007,
Pubmed
Mulugeta,
Processing of surfactant protein C requires a type II transmembrane topology directed by juxtamembrane positively charged residues.
2003,
Pubmed
Ouali,
Cascaded multiple classifiers for secondary structure prediction.
2000,
Pubmed
Ovaere,
The emerging roles of serine protease cascades in the epidermis.
2009,
Pubmed
Passero,
New role for plasmin in sodium homeostasis.
2010,
Pubmed
Pickering,
Palmitoylation of the GluR6 kainate receptor.
1995,
Pubmed
Pochynyuk,
Purinergic control of apical plasma membrane PI(4,5)P2 levels sets ENaC activity in principal cells.
2008,
Pubmed
Pochynyuk,
Regulation of the epithelial Na+ channel (ENaC) by phosphatidylinositides.
2006,
Pubmed
Pochynyuk,
Identification of a functional phosphatidylinositol 3,4,5-trisphosphate binding site in the epithelial Na+ channel.
2005,
Pubmed
Pochynyuk,
Molecular determinants of PI(4,5)P2 and PI(3,4,5)P3 regulation of the epithelial Na+ channel.
2007,
Pubmed
Pochynyuk,
Binding and direct activation of the epithelial Na+ channel (ENaC) by phosphatidylinositides.
2007,
Pubmed
Qanbar,
Role of palmitoylation/depalmitoylation reactions in G-protein-coupled receptor function.
2003,
Pubmed
Qin,
Unique regulatory properties of the type 2a Ca2+ channel beta subunit caused by palmitoylation.
1998,
Pubmed
,
Xenbase
Rossier,
Activation of the epithelial sodium channel (ENaC) by serine proteases.
2009,
Pubmed
Ruffieux-Daidié,
Deubiquitylation regulates activation and proteolytic cleavage of ENaC.
2008,
Pubmed
Sheng,
Epithelial sodium channel pore region. structure and role in gating.
2001,
Pubmed
,
Xenbase
Sheng,
Furin cleavage activates the epithelial Na+ channel by relieving Na+ self-inhibition.
2006,
Pubmed
,
Xenbase
Snyder,
Gating induces a conformational change in the outer vestibule of ENaC.
2000,
Pubmed
,
Xenbase
Snyder,
A pore segment in DEG/ENaC Na(+) channels.
1999,
Pubmed
Suzuki,
Formation of aquaporin-4 arrays is inhibited by palmitoylation of N-terminal cysteine residues.
2008,
Pubmed
Tian,
Palmitoylation gates phosphorylation-dependent regulation of BK potassium channels.
2008,
Pubmed
Tsutsumi,
Discovery of protein-palmitoylating enzymes.
2008,
Pubmed
Valdez-Taubas,
Swf1-dependent palmitoylation of the SNARE Tlg1 prevents its ubiquitination and degradation.
2005,
Pubmed
Valentijn,
Biosynthesis and processing of epithelial sodium channels in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Weisz,
Non-coordinate regulation of endogenous epithelial sodium channel (ENaC) subunit expression at the apical membrane of A6 cells in response to various transporting conditions.
2000,
Pubmed
,
Xenbase
Yang,
Palmitoylation supports assembly and function of integrin-tetraspanin complexes.
2004,
Pubmed
Yik,
Nonpalmitoylated human asialoglycoprotein receptors recycle constitutively but are defective in coated pit-mediated endocytosis, dissociation, and delivery of ligand to lysosomes.
2002,
Pubmed
Yue,
Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates epithelial sodium channel activity in A6 cells.
2002,
Pubmed
,
Xenbase
