Walther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Medical Faculty, LMU-Munich, Munich, Germany.
Department of Pathology, New York University School of Medicine, New York, NY, 10016, USA.
Sci Rep. 2020 Apr 22;10(1):6812. doi: 10.1038/s41598-020-63677-2.
Stromal interaction molecules (STIM1, 2) are acting as sensors for Ca in intracellular stores and activate Orai channels at the plasma membrane for store-operated Ca entry (SOCE), while classical transient receptor potential (TRPC) channel mediate receptor-operated Ca entry (ROCE). Several reports, however, indicate a role for TRPC in SOCE in certain cell types. Here, we analyzed Ca influx and cell function in TRPC1/6-deficient (TRPC1/6) and STIM1/2- deficient (STIM1/2) primary murine lung fibroblasts (pmLF). As expected, SOCE was decreased in STIM1/2- deficient pmLF and ROCE was decreased in TRPC1/6 pmLF compared to control cells. By contrast, SOCE was not significantly different in TRPC1/6 pmLF and ROCE was similar in STIM1/2-deficient pmLF compared to Wt cells. Most interestingly, cell proliferation, migration and nuclear localization of nuclear factor of activated T-cells (NFATc1 and c3) were decreased after ablation of STIM1/2 proteins in pmLF. In conclusion, TRPC1/6 channels are not involved in SOCE and STIM1/2 deficiency resulted in decreased cell proliferation and migration in pmLF.
基质相互作用分子（STIM1、2）作为细胞内储存钙离子的传感器，激活质膜上的 Orai 通道，从而实现储存操作的钙离子内流（SOCE），而经典瞬时受体电位（TRPC）通道介导受体操作的钙离子内流（ROCE）。然而，有几项报道表明，在某些细胞类型中，TRPC 参与 SOCE。在这里，我们分析了 TRPC1/6 缺陷（TRPC1/6）和 STIM1/2 缺陷（STIM1/2）的原代小鼠肺成纤维细胞（pmLF）中的钙离子内流和细胞功能。如预期的那样，与对照细胞相比，STIM1/2 缺陷的 pmLF 中的 SOCE 减少，而 TRPC1/6 pmLF 中的 ROCE 减少。相比之下，与 WT 细胞相比，TRPC1/6 pmLF 中的 SOCE 没有显著差异，而 STIM1/2 缺陷的 pmLF 中的 ROCE 相似。最有趣的是，在 pmLF 中敲除 STIM1/2 蛋白后，活化 T 细胞核因子（NFATc1 和 c3）的细胞增殖、迁移和核定位减少。总之，TRPC1/6 通道不参与 SOCE，STIM1/2 缺乏导致 pmLF 中的细胞增殖和迁移减少。
