Ca2+ protein alpha 1D of CaV1.3 regulates intracellular calcium concentration and migration of colon cancer cells through a non-canonical activity - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2017

Ca2+ protein alpha 1D of CaV1.3 regulates intracellular calcium concentration and migration of colon cancer cells through a non-canonical activity

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It is generally accepted that voltage-gated Ca2+ channels, CaV, regulate Ca2+ homeostasis in excitable cells following plasma membrane depolarization. Here, we show that the Ca2+ protein α1D of CaV1.3 channel is overexpressed in colorectal cancer biopsies compared to normal tissues. Gene silencing experiments targeting α1D reduced the migration and the basal cytosolic Ca2+ concentration of HCT116 colon cancer cell line and modified the cytosolic Ca2+ oscillations induced by the sodium/calcium exchanger NCX1/3 working in its reverse mode. Interestingly, NCX1/3 regulated membrane potential of HCT116 cells only when α1D was silenced, and blocking NCX1/3 increased cytosolic Ca2+ concentration and cell migration. However, membrane depolarization did not induce an increase in intracellular Ca2+. Patch-clamp experiments clearly showed that the inward Ca2+ current was absent. Finally, flow cytometry and immunofluorescence studies showed that α1D protein was localized at the plasma membrane, in cytosol and cell nuclei. Altogether, we uncover a novel signaling pathway showing that α1D is involved in the regulation of Ca2+ homeostasis and cell migration by a mechanism independent of its plasma membrane canonical function but that involved plasma membrane Na+/Ca2+ exchanger.
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hal-01705171 , version 1 (17-11-2022)

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Yann Fourbon, Maxime Guéguinou, Romain Félix, Bruno Constantin, Arnaud Uguen, et al.. Ca2+ protein alpha 1D of CaV1.3 regulates intracellular calcium concentration and migration of colon cancer cells through a non-canonical activity. Scientific Reports, 2017, 7 (1), pp.14199. ⟨10.1038/s41598-017-14230-1⟩. ⟨hal-01705171⟩
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