Biology Department Seminar

The collecting duct is the final site of acid base regulation in the kidney. Intercalated cells of the cortical collecting duct mediate acid-base transport with the help of chloride-bicarbonate exchanger proteins AE1 , pendrin and Proton pump (Vacuolar ATPase). Two functionally and morphologically distinct intercalated cells have been identified in the kidney: one secretes bicarbonate (beta-intercalated cell) and the other absorbs bicarbonate (alpha-intercalated cells). Using rabbits that were fed an acid diet, we observed that chronic metabolic acidosis remodels the bicarbonate secreting beta-intercalated to convert to beta-intercalated cells. Rabbit beta-intercalated cell line (Clone C) when seeded at high density undergoes extensive cytoskeletal remodeling and exhibits functional characteristics of beta intercalated cells. We indentified a novel multidomain protein named hensin that deposited in the extracellular matrix (ECM) of high density Clone C cells to be the key player in this phenotypic remodeling. Subsequently, we have identified that a multifunctional sugar binding protein, galectin-3 interacts with hensin and this interaction is critical for the ECM assembly of hensin. Furthermore ECM polymerization requires activation of integrin beta1 and hensin's interaction with integrin beta1. The exciting part of our discovery is that hensin mediated phenotypic conversion may reflect a more general role of hensin-galectin-3-integrin beta1 in the terminal differentiation of all epithelia. We observed that the hensin and galectin-3 localization is significantly different in the terminally differentiated villus cells of the small intestine and the luminal cells of the prostate compared to the less differentiated crypt cells and basal cells. This talk will summarize the past work performed in our laboratory and outline some of the current work that is in progress.