Topic Overview:

The epithelial sodium channel (ENaC) is the rate-limiting entry step in the movement of sodium across epithelial tissues and is a major determinant in salt and water reabsorption across the kidney distal nephron. Abnormalities in ENaC function have been linked to several human diseases associated with altered salt and water balance. These diseases include proteinuric chronic kidney disease, the salt-wasting disorder pseudohypoaldosteronism, nephrosis, pulmonary edema, and cystic fibrosis. More significantly, alterations in ENaC activity have been linked to forms of salt-sensitive hypertension, a condition that affects up to 30 percent of Americans and more than 1.2 billion people worldwide.

Butterworth’s research focuses on the role of protein trafficking and recycling in ENaC regulation. Using a multidisciplinary approach, his team characterized trafficking of endogenously expressed ENaC in principal cells of the kidney collecting duct. Their ongoing studies aim to map the itinerary of ENaC from synthesis to destruction. Thus far, they have: (1) identified the mechanisms of ENaC internalization from the apical surface of epithelial cells, (2) demonstrated the requirement for a de-ubiquitinylating enzyme that facilitates ENaC recycling, and (3) Characterized the role of the small GTPase Rab11b in regulated recycling of the channel.

More recent efforts have focused on understanding the underlying regulation of these trafficking events and include investigations into the role of microRNAs in the hormonal control of sodium transport. In this seminar, Butterworth will follow ENaC’s journey through an epithelial cell and demonstrate how an understanding of the basic cell biology of ENaC trafficking may provide insights into the misregulation associated with disease.