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

Elena Kleymenova, Oxana Ibraghimov-Beskrovnaya, Hiroyuki Kugoh, Jeff Everitt, Hui Xu, Kaoru Kiguchi, Greg Landes, Peter Harris, Cheryl Walker

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)823-832
Number of pages10
JournalMolecular Cell
Volume7
Issue number4
DOIs
StatePublished - Apr 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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