Store-operated Ca2+ entry in primary murine lung fibroblasts is independent of classical transient receptor potential (TRPC) channels and contributes to cell migration
Store-operated Ca2+ entry in primary murine lung fibroblasts is independent of classical transient receptor potential (TRPC) channels and contributes to cell migration
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DOI：
10.1038/s41598-020-63677-2
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发表时间：
2020-04-22
影响因子：
4.6
通讯作者：
Dietrich, Alexander
中科院分区：
文献类型：
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作者：
Bendiks, Larissa;Geiger, Fabienne;Dietrich, Alexander
基质相互作用分子（Stromal interaction molecules，STIM 1，2）作为细胞内钙库中钙离子的传感器，激活质膜上的奥赖通道，进行钙库操纵的钙离子内流（store-operated Ca 2 + entry，SOCE），而经典的瞬时受体电位（transmittent receptor potential，TRPC）通道介导受体操纵的钙离子内流（receptor-operated Ca 2 + entry，ROCE）。然而，一些报告表明TRPC在某些细胞类型的SOCE中的作用。在此，我们分析了TRPC 1/6缺陷型（TRPC 1/6（-/-））和STIM 1/2缺陷型（STIM 1/2（Delta pmLF））原代鼠肺成纤维细胞（pmLF）中的Ca 2+内流和细胞功能。正如预期的那样，与对照细胞相比，STIM 1/2缺陷型pmLF中的SOCE降低，TRPC 1/6（-/-）pmLF中的ROCE降低。相比之下，与Wt细胞相比，TRPC 1/6（-/-）pmLF中的SOCE没有显著差异，STIM 1/2缺陷pmLF中的ROCE相似。最有趣的是，细胞增殖，迁移和活化的T细胞（NFATc 1和c3）的核因子的核定位减少后，在pmLF中的STIM 1/2蛋白消融。总之，TRPC 1/6通道不参与SOCE，STIM 1/2缺陷导致pmLF细胞增殖和迁移降低。
Stromal interaction molecules (STIM1, 2) are acting as sensors for Ca2+ in intracellular stores and activate Orai channels at the plasma membrane for store-operated Ca2+ entry (SOCE), while classical transient receptor potential (TRPC) channel mediate receptor-operated Ca2+ entry (ROCE). Several reports, however, indicate a role for TRPC in SOCE in certain cell types. Here, we analyzed Ca2+ influx and cell function in TRPC1/6-deficient (TRPC1/6(-/-)) and STIM1/2- deficient (STIM1/2(Delta pmLF)) 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.