Heterologous calcium-dependent inactivation of Orai1 by neighboring TRPV1 channels modulates cell migration and wound healing

• Published in: Communications biology Vol. 2; no. 1; p. 88
• Main Authors: Bastián-Eugenio, Carlos Ernesto, Bohórquez-Hernández, Arlette, Pacheco, Jonathan, Sampieri, Alicia, Asanov, Alexander, Ocelotl-Oviedo, Jose Pablo, Guerrero, Adán, Darszon, Alberto, Vaca, Luis
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.03.2019; Nature Publishing Group
• Subjects: 14/19; 14/33; 631/57; 631/80; 82/79; 9/74; 96/35; 96/63; Biology; Biomedical and Life Sciences; Calcium - metabolism; Calcium channels; Calcium influx; Calcium Signaling; Capsaicin receptors; Cell adhesion & migration; Cell membranes; Cell migration; Cell Movement - genetics; Cells, Cultured; Electrophysiological Phenomena; Gene Expression; Genes, Reporter; Humans; Life Sciences; Orai1 protein; ORAI1 Protein - metabolism; Recombinant Fusion Proteins - metabolism; Thrombin; TRPV Cation Channels - metabolism; Wound Healing
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-019-0338-1

Store-operated calcium entry (SOCE) is an essential calcium influx mechanism in animal cells. One of the most important auto regulatory control systems involves calcium-dependent inactivation (CDI) of the Orai channel, which prevents excessive calcium influx. In the present study we analyze the role of two channels in the induction of CDI on Orai1. Here we show that calcium entering through freely diffusing TRPV1 channels induce strong CDI on Orai1 while calcium entering through P2X 4 channel does not. TRPV1 can induce CDI on Orai1 because both channels were found in close proximity in the cell membrane. This was not observed with P2X 4 channels. To our knowledge, this is the first study demonstrating that calcium arising from different channels may contribute to the modulation of Orai1 through CDI in freely diffusing single channels of living cells. Our results highlight the role of TRPV1-mediated CDI on Orai1 in cell migration and wound healing. Bastián-Eugenio et al. showed that calcium entering the cell via TRPV1, but not P2X 4 channels, can induce calcium-dependent inactivation of Orai1. This inactivation impacts thrombin-induced cell migration and wound healing suggesting an important role of Orai1 modulation by TRPV1 channels.