Project 170530

The acid-base balance of organisms, including humans, must be carefully regulated. Both the pH (a measure of the concentration of acid) of cells and of the fluids that bathe them, including blood, are continuously challenged, yet maintained within very narrow boundaries. This exquisite regulation is attributable to a family of molecules that transport acid or base across the cell membranes. Among the most active and important transporters are the sodium/proton exchangers, a family of 9 different types of molecules widely distributed throughout the body. Several of these have been linked to various types of neurological, vascular and renal disease. The work described in this proposal has three separate aims: 1) Understanding how one of the prototypical sodium/proton exchangers, NHE3, interacts with and is regulated by the charge of the cell membrane; 2) To use yeast as a vehicle to express and study the NHE6-9 exchangers, which have proven otherwise intractable and 3) To devise and implement a method to study the electrical potential that develops across the membrane of endosomes, organelles that carry cargo into the cells. This fundamental knowledge will contribute to our understanding and eventual treatment of disease.

devise and implement a method to study the electrical potential that develops across the membrane of endosomes