Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characte rized by hamartomas in multiple organs, notably the brain and kidneys. The disease is caused by mutations in TSC1 or TSC2 genes, coding hamartin and t uberin, respectively. Immunofluorescence analysis of tuberin and hamartin p erformed here demonstrates that both proteins are specifically expressed in the distal urinary tubule, comprising the distal tubules, connecting segme nt, and collecting ducts. Hamartin, distinct from tuberin, is expressed in the thick ascending limbs of Henle and in juxtaglomerular cells, where it c olocalizes with renin. In positive epithelial cells, tuberin localizes to t he cytoplasm as well as the apical membrane. Hamartin, however, preferentia lly localizes to the apical membrane. The two proteins colocalize at the ap ical membrane of type A intercalated cells and connecting tubule cells, whe reas in type B intercalated cells they reveal a variable pattern of express ion. The cell-specific expression of tuberin and hamartin described here wi ll provide critical insight into the cell types that give rise to kidney le sions, and the tumor suppressor role of these proteins in TSC.