Tuberin-dependent membrane localization of polycystin-1: a functional link between polycystic kidney disease and the TSC2 tumor suppressor gene.

Published

Journal Article

The PKD1 gene accounts for 85% of autosomal dominant polycystic kidney disease (ADPKD), the most common human genetic disorder. Rats with a germline inactivation of one allele of the Tsc2 tumor suppressor gene developed early onset severe bilateral polycystic kidney disease, with similarities to the human contiguous gene syndrome caused by germline codeletion of PKD1 and TSC2 genes. Polycystic rat renal cells retained two normal Pkd1 alleles but were null for Tsc2 and exhibited loss of lateral membrane-localized polycystin-1. In tuberin-deficient cells, intracellular trafficking of polycystin-1 was disrupted, resulting in sequestration of polycystin-1 within the Golgi and reexpression of Tsc2 restored correct polycystin-1 membrane localization. These data identify tuberin as a determinant of polycystin-1 functional localization and, potentially, ADPKD severity.

Full Text

Duke Authors

Cited Authors

  • Kleymenova, E; Ibraghimov-Beskrovnaya, O; Kugoh, H; Everitt, J; Xu, H; Kiguchi, K; Landes, G; Harris, P; Walker, C

Published Date

  • April 2001

Published In

Volume / Issue

  • 7 / 4

Start / End Page

  • 823 - 832

PubMed ID

  • 11336705

Pubmed Central ID

  • 11336705

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/s1097-2765(01)00226-x

Language

  • eng