Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells

G. Aguiari, V. Trimi, M. Bogo, A. Mangolini, G. Szabadkai, P. Pinton, R. Witzgall, Peter C Harris, P. A. Borea, R. Rizzuto, L. Del Senno

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)554-573
Number of pages20
JournalCell Proliferation
Volume41
Issue number3
DOIs
StatePublished - Jun 2008

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Calcium Signaling
Cell Proliferation
Kidney
Autosomal Dominant Polycystic Kidney
Homeostasis
Cystic Kidney Diseases
NFATC Transcription Factors
HEK293 Cells
RNA Interference
polycystic kidney disease 1 protein
Cations
Cell Cycle
Cell Line
Serum

ASJC Scopus subject areas

  • Cell Biology

Cite this

Aguiari, G., Trimi, V., Bogo, M., Mangolini, A., Szabadkai, G., Pinton, P., ... Del Senno, L. (2008). Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells. Cell Proliferation, 41(3), 554-573. https://doi.org/10.1111/j.1365-2184.2008.00529.x

Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells. / Aguiari, G.; Trimi, V.; Bogo, M.; Mangolini, A.; Szabadkai, G.; Pinton, P.; Witzgall, R.; Harris, Peter C; Borea, P. A.; Rizzuto, R.; Del Senno, L.

In: Cell Proliferation, Vol. 41, No. 3, 06.2008, p. 554-573.

Research output: Contribution to journalArticle

Aguiari, G, Trimi, V, Bogo, M, Mangolini, A, Szabadkai, G, Pinton, P, Witzgall, R, Harris, PC, Borea, PA, Rizzuto, R & Del Senno, L 2008, 'Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells', Cell Proliferation, vol. 41, no. 3, pp. 554-573. https://doi.org/10.1111/j.1365-2184.2008.00529.x
Aguiari, G. ; Trimi, V. ; Bogo, M. ; Mangolini, A. ; Szabadkai, G. ; Pinton, P. ; Witzgall, R. ; Harris, Peter C ; Borea, P. A. ; Rizzuto, R. ; Del Senno, L. / Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells. In: Cell Proliferation. 2008 ; Vol. 41, No. 3. pp. 554-573.
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