Membrane Biology
Acetylation Stimulates the Epithelial Sodium Channel by Reducing Its Ubiquitination and Degradation
Background:The epithelial Na+ channel ENaC plays an important role in epithelial Na+ absorption.Results:Lysine acetylation increased ENaC abundance and current by antagonizing its ubiquitination and degradation.Conclusion:Acetylation regulates ENaC stability.Significance:Lysine modification plays a central role in ENaC regulation, where it may contribute to the control of Na+ homeostasis and blood pressure.Intracellular Na+ Regulates Epithelial Na+ Channel Maturation
Epithelial Na+ channel (ENaC) function is regulated by the intracellular Na+ concentration ((Na+)i) through a process known as Na+ feedback inhibition. Although this process is known to decrease the expression of proteolytically processed active channels on the cell surface, it is unknown how (Na+)i alters ENaC cleavage. We show here that (Na+)i regulates the posttranslational processing of ENaC subunits during channel biogenesis. At times when (Na+)i is low, ENaC subunits develop mature N-glycans and are processed by proteases.Proteolytic Regulation of Epithelial Sodium Channels by Urokinase Plasminogen Activator: CUTTING EDGE AND CLEAVAGE SITES
Plasminogen activator inhibitor 1 (PAI-1) level is extremely elevated in the edematous fluid of acutely injured lungs and pleurae. Elevated PAI-1 specifically inactivates pulmonary urokinase-type (uPA) and tissue-type plasminogen activators (tPA). We hypothesized that plasminogen activation and fibrinolysis may alter epithelial sodium channel (ENaC) activity, a key player in clearing edematous fluid. Two-chain urokinase (tcuPA) has been found to strongly stimulate heterologous human αβγ ENaC activity in a dose- and time-dependent manner.
