Open AccessNovel role for polycystin‐1 in modulating cell proliferation through calcium oscillations in kidney cells
Author(s) -
Aguiari G.,
Trimi V.,
Bogo M.,
Mangolini A.,
Szabadkai G.,
Pinton P.,
Witzgall R.,
Harris P. C.,
Borea P. A.,
Rizzuto R.,
Del Senno L.
Publication year - 2008
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2008.00529.x
Subject(s) - cell growth , microbiology and biotechnology , homeostasis , hek 293 cells , polycystic kidney disease , cell , biology , endogeny , kidney , medicine , receptor , endocrinology , biochemistry
. Objectives : Polycystin‐1 (PC1), a signalling receptor regulating Ca 2+ ‐permeable cation channels, is mutated in autosomal dominant polycystic kidney disease, which is typically characterized by increased cell proliferation. However, the precise mechanisms by which PC1 functions on Ca 2+ homeostasis, signalling and cell proliferation remain unclear. Here, we investigated the possible role of PC1 as a modulator of non‐capacitative Ca 2+ entry (NCCE) and Ca 2+ oscillations, with downstream effects on cell proliferation. Results and discussion : By employing RNA interference, we show that depletion of endogenous PC1 in HEK293 cells leads to an increase in serum‐induced Ca 2+ oscillations, triggering nuclear factor of activated T cell activation and leading to cell cycle progression. Consistently, Ca 2+ oscillations and cell proliferation are increased in PC1‐mutated kidney cystic cell lines, but both abnormal features are reduced in cells that exogenously express PC1. Notably, blockers of the NCCE pathway, but not of the CCE, blunt abnormal oscillation and cell proliferation. Our study therefore provides the first demonstration that PC1 modulates Ca 2+ oscillations and a molecular mechanism to explain the association between abnormal Ca 2+ homeostasis and cell proliferation in autosomal dominant polycystic kidney disease.