Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico.
TIRF Labs Inc., 106 Grendon Place, Cary, 27519, NC, USA.
Commun Biol. 2019 Mar 4;2:88. doi: 10.1038/s42003-019-0338-1. eCollection 2019.
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 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 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.
钙库操纵性钙内流（SOCE）是动物细胞中一种重要的钙离子内流机制。最重要的自动调节控制系统之一涉及到钙依赖性失活（CDI）的 Orai 通道，这可以防止过多的钙离子内流。在本研究中，我们分析了两种通道在诱导 Orai1 上 CDI 的作用。在这里，我们表明，通过自由扩散的 TRPV1 通道进入的钙可以强烈诱导 Orai1 的 CDI，而通过 P2X 通道进入的钙则不会。TRPV1 可以诱导 Orai1 的 CDI，因为这两种通道在细胞膜上非常接近。这在 P2X 通道中没有观察到。据我们所知，这是第一个研究表明，来自不同通道的钙可能通过活细胞中自由扩散的单个通道中的 CDI 对 Orai1 进行调节。我们的研究结果强调了 TRPV1 介导的 Orai1 上的 CDI 在细胞迁移和伤口愈合中的作用。
