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Assembly and Trafficking of the Epithelial Sodium Channel

 

The epithelial sodium channel (ENaC) is made up of three homologous subunits ( a , b , and g ). Although the channel can assemble in multiple combinations, the fully active form is thought to exist as an a 2 bg heterotetramer.

Defects in this channel result in hypertension disorders such as Liddle's syndrome. Although the channel subunits have been cloned, little is known about the expression or regulation of this channel in the kidney. Regulation of ENaC activity is complex, and is modulated by changes in transcription, translation, and intracellular trafficking.

Our long term objective is to determine the factors that regulate the synthesis, apical membrane insertion and recycling of ENaC under varying conditions of transepithelial transport in polarized epithelial cells. We have found that individual ENaC subunits have distinct rates of turnover from the cell surface and may traffic differentially. We have proposed two general models to explain this novel paradigm of non-coordinate regulation of ENaC subunit modulation. In the first model, differential trafficking of subsets of these channels accounts for regulation of Na + transport.

In the second model, holochannel assembly and activity can be reversibly modulated at or near the apical membrane by removal or insertion of individual subunits.   Current experiments are underway to discriminate between these models in polarized renal cells that express heterologous and endogenous ENaC subunits.

Apical Membrane Traffic »
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