T R Kleyman


Affiliation: University of Pittsburgh
Country: USA


  1. Kleyman T, Kashlan O, Hughey R. Epithelial Na+ Channel Regulation by Extracellular and Intracellular Factors. Annu Rev Physiol. 2018;80:263-281 pubmed publisher
    ..It also addresses other factors, including acidic phospholipids and modification of ENaC cytoplasmic cysteine residues by palmitoylation, which enhance channel activity by altering interactions of the channel with the plasma membrane. ..
  2. Sheng S, Chen J, Mukherjee A, Yates M, Buck T, Brodsky J, et al. Thumb domains of the three epithelial Na+ channel subunits have distinct functions. J Biol Chem. 2018;293:17582-17592 pubmed publisher
  3. Shi S, Mutchler S, Blobner B, Kashlan O, Kleyman T. Pore-lining residues of MEC-4 and MEC-10 channel subunits tune the Caenorhabditis elegans degenerin channel's response to shear stress. J Biol Chem. 2018;293:10757-10766 pubmed publisher
    ..Our results suggest that pore-lining residues of MEC-4 and MEC-10 have important yet different roles in tuning the channel's response to mechanical forces. ..
  4. Chen J, Ray E, Yates M, Buck T, Brodsky J, Kinlough C, et al. Functional Roles of Clusters of Hydrophobic and Polar Residues in the Epithelial Na+ Channel Knuckle Domain. J Biol Chem. 2015;290:25140-50 pubmed publisher
    ..Our results suggest that multiple residues in the α subunit knuckle domain contribute to the mechanism of Na(+) self-inhibition by interacting with palm and finger domain residues via two separate and chemically distinct motifs. ..
  5. Webb T, Carrisoza Gaytán R, Montalbetti N, Rued A, Roy A, Socovich A, et al. Cell-specific regulation of L-WNK1 by dietary K. Am J Physiol Renal Physiol. 2016;310:F15-26 pubmed publisher
    ..A high-K(+) diet induced an increase in L-WNK1 expression selectively in intercalated cells and may contribute to enhanced BK channel expression and K(+) secretion in CCDs. ..
  6. Mukherjee A, Wang Z, Kinlough C, Poland P, Marciszyn A, Montalbetti N, et al. Specific Palmitoyltransferases Associate with and Activate the Epithelial Sodium Channel. J Biol Chem. 2017;292:4152-4163 pubmed publisher
    ..Treatment of polarized mCCDcl1 cells with a general inhibitor of palmitoylation reduced ENaC-mediated Na+ currents within minutes. Our results indicate that specific DHHCs have a role in regulating ENaC. ..
  7. Shi S, Kleyman T. Gamma subunit second transmembrane domain contributes to epithelial sodium channel gating and amiloride block. Am J Physiol Renal Physiol. 2013;305:F1585-92 pubmed publisher
    ..In summary, we have identified novel pore-lining residues of the ?-subunit of ENaC that are important for proper channel gating and its interaction with amiloride. ..
  8. Mukherjee A, Mueller G, Kinlough C, Sheng N, Wang Z, Mustafa S, et al. Cysteine palmitoylation of the ? subunit has a dominant role in modulating activity of the epithelial sodium channel. J Biol Chem. 2014;289:14351-9 pubmed publisher
    ..Comparison of activities of channels lacking palmitoylation sites in individual or multiple subunits revealed that ? subunit palmitoylation has a dominant role over ? subunit palmitoylation in modulating ENaC gating. ..
  9. Shi S, Luke C, Miedel M, Silverman G, Kleyman T. Activation of the Caenorhabditis elegans Degenerin Channel by Shear Stress Requires the MEC-10 Subunit. J Biol Chem. 2016;291:14012-22 pubmed publisher
    ..Our findings suggest that MEC-10 has an important role in the channel's response to mechanical forces. ..

More Information


  1. request reprint
    Kleyman T, Zuckerman J, Middleton P, McNulty K, Hu B, Su X, et al. Cell surface expression and turnover of the alpha-subunit of the epithelial sodium channel. Am J Physiol Renal Physiol. 2001;281:F213-21 pubmed
    ..3-fold increase in short-circuit current. This lack of change in surface expression is consistent with previous observations in A6 cells and suggests that aldosterone regulates ENaC gating and increases channel open probability...
  2. Agrawal P, Wang R, Li H, Schmitz Abe K, Simone Roach C, Chen J, et al. The Epithelial Sodium Channel Is a Modifier of the Long-Term Nonprogressive Phenotype Associated with F508del CFTR Mutations. Am J Respir Cell Mol Biol. 2017;57:711-720 pubmed publisher
    ..Our data suggest a potential role for δ-ENaC in controlling sodium reabsorption in the airways, and advance the plausibility of ENaC as a therapeutic target in CF. ..
  3. Shi S, Buck T, Kinlough C, Marciszyn A, Hughey R, Chalfie M, et al. Regulation of the epithelial Na+ channel by paraoxonase-2. J Biol Chem. 2017;292:15927-15938 pubmed publisher
    ..Together, our data suggest that PON-2 regulates ENaC activity by modulating its intracellular trafficking and surface expression. ..