Retention of membrane‐localized β‐catenin in cells lacking functional polycystin‐1 and tuberin

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Abstract
The tuberous sclerosis (TSC) 2 tumor suppressor gene encodes the protein tuberin, which has recently been shown to play a crucial role in the intracellular trafficking of polycystin‐1, the product of the polycystic kidney disease (PDK) 1 gene. PKD1 is responsible for most cases of autosomal dominant polycystic kidney disease, which has been described as “neoplasia in disguise.” Polycystin‐1 is a membrane protein localized to adherens junctions in a complex containing E‐cadherin and α‐, β‐, and γ‐catenins. To determine whether loss of membrane localization of polycystin‐1 and E‐cadherin affects the function of β‐catenin, β‐catenin localization and signaling were characterized in tuberin‐null EKT2 and ERC15 cells and in tuberin‐positive TRKE2 cells derived from polycystic, neoplastic, and normal rat kidney epithelial cells, respectively. EKT2 cells lacking tuberin because of inactivation of the Tsc2 gene fail to localize polycystin‐1 and E‐cadherin appropriately to these junctions. However, β‐catenin was retained at lateral cell membranes in both tuberin‐null and tuberin‐positive cells. Moreover, gene transcription mediated by β‐catenin T‐cell–specific transcription factor complexes showed no differences among EKT2, ERC15, and TRKE2 cells. Thus, β‐catenin was stably retained at the lateral cell membrane in tuberin‐null renal cells lacking membrane‐localized polycystin‐1 and E‐cadherin. These data suggest that, although loss of Tsc2 tumor suppressor gene function disrupts normal polycystin‐1 function and membrane localization of E‐cadherin, normal β‐catenin signaling is retained in tuberin‐null cells.