Alan S. L. Yu, MB, BChir
The primary goal of my research program is to understand the mechanisms of renal tubule salt and water transport and how disorders in these lead to the development of hypertension. Currently a major focus of our laboratory is on a family of membrane proteins called claudins that play critical roles in the barrier and permeability functions of the tight junction. Our lab has meticulously mapped out the localization of claudins along the renal tubule and developed a series of electrophysiological techniques to investigate the ionic permeability of claudin pores and to dissect out the functional effects of claudin overexpression in the setting of compensatory changes in the endogenous tight junction composition. Our recent work has focused on structure-function studies of the claudin-2 pore. We reported the first quantitative measurements of the macroscopic conductance and selectivity of a claudin pore and identified the cation-binding site responsible for determining charge selectivity. We have also begun to use cysteine scanning mutagenesis to probe the architecture of the first extracellular loop and gain insights into claudin stoichiometry.