Aguiari, G. and Trimi, V. and Bogo, M. and Mangolini, A. and Szabadkai, G. and Pinton, P. and Witzgall, R. and Harris, P. C. and Borea, P. A. and Rizzuto, R. and del Senno, L. (2008) Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells. CELL PROLIFERATION, 41 (3). pp. 554-573. ISSN 0960-7722, 1365-2184
Full text not available from this repository. (Request a copy)Abstract
Objectives: Polycystin-1 (PC1), a signalling receptor regulating Ca2+-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 Ca2+ homeostasis, signalling and cell proliferation remain unclear. Here, we investigated the possible role of PC1 as a modulator of non-capacitative Ca2+ entry (NCCE) and Ca2+ 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 Ca2+ oscillations, triggering nuclear factor of activated T cell activation and leading to cell cycle progression. Consistently, Ca2+ 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 Ca2+ oscillations and a molecular mechanism to explain the association between abnormal Ca2+ homeostasis and cell proliferation in autosomal dominant polycystic kidney disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | C-TERMINAL FRAGMENT; SMOOTH-MUSCLE-CELLS; RECIPROCAL REGULATION; SIGNALING PATHWAY; EPITHELIAL-CELLS; BRANCHING MORPHOGENESIS; CHANNEL ACTIVITY; MAMMALIAN-CELLS; CATION CHANNEL; NITRIC-OXIDE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie > Prof. Dr. Ralph Witzgall |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Oct 2020 11:53 |
| Last Modified: | 29 Oct 2020 11:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30773 |
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