TY - JOUR
T1 - Tuberin-dependent membrane localization of polycystin-1
T2 - A functional link between polycystic kidney disease and the TSC2 tumor suppressor gene
AU - Kleymenova, Elena
AU - Ibraghimov-Beskrovnaya, Oxana
AU - Kugoh, Hiroyuki
AU - Everitt, Jeff
AU - Xu, Hui
AU - Kiguchi, Kaoru
AU - Landes, Greg
AU - Harris, Peter
AU - Walker, Cheryl
N1 - Funding Information:
We thank Drs. E. Henske, W. Brown, and D. Hunter for critical review of this manuscript and helpful suggestions. This work was supported by National Institutes of Health grants CA 63613 (to C. L. W.) and CA 16672 (to MD Anderson Cancer Center) and National Institute of Environmental Health Sciences Grant ES07784.
PY - 2001/4
Y1 - 2001/4
N2 - 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.
AB - 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.
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U2 - 10.1016/S1097-2765(01)00226-X
DO - 10.1016/S1097-2765(01)00226-X
M3 - Article
C2 - 11336705
AN - SCOPUS:0035019467
SN - 1097-2765
VL - 7
SP - 823
EP - 832
JO - Molecular Cell
JF - Molecular Cell
IS - 4
ER -