TRPC1 contributes to the Ca2+-dependent regulation of adenylate cyclases.
TRPC1 contributes to the Ca2+-dependent regulation of adenylate cyclases.
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DOI：
10.1042/bj20140766
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发表时间：
2014-11-15
期刊：
影响因子：
--
通讯作者：
Cooper DM
中科院分区：
文献类型：
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作者：
Willoughby D;Ong HL;De Souza LB;Wachten S;Ambudkar IS;Cooper DM
SOCE（储存操作的Ca2+进入）是通过特定的质膜通道介导的，以响应内质网Ca2+储存耗尽。这条Ca2+进入途径是Ca2+和cAMP信号在调节Ca2+敏感腺苷酸环化酶（AC1, AC5， AC6和AC8）活性中的动态相互作用的核心。两种蛋白质已被确定为SOCE的关键成分：STIM1（基质相互作用分子1），它感知ER Ca2+储存含量，并在储存耗尽时转运到质膜，然后激活Orai1，即CRAC （Ca2+释放激活Ca2+）通道的成孔成分。先前的研究报道，在HEK-293（人胚胎肾293）细胞中，STIM1和Orai1的共表达增强了Ca2+刺激的AC8活性，并且AC8和Orai1直接相互作用增强了这种调节。尽管如此，也有人提出了TRPC（瞬时受体电位规范）通道在SOCE中的额外参与。在本研究中，我们评估了TRPC1在稳定表达AC8 （HEK-AC8）的HEK-293细胞和表达内源性Ca2+抑制AC6的HSG（人颌下腺）细胞中soce介导的Ca2+敏感ACs的调节中的作用。我们证明了TRPC1作为SOCE的一个组成部分，与STIM1和Orai1一起，在调节AC微域内的Ca2+通量和影响cAMP的产生中发挥作用。
SOCE (store-operated Ca2+ entry) is mediated via specific plasma membrane channels in response to ER (endoplasmic reticulum) Ca2+ store depletion. This route of Ca2+ entry is central to the dynamic interplay between Ca2+ and cAMP signalling in regulating the activity of Ca2+ -sensitive adenylate cyclase isoforms (AC1, AC5, AC6 and AC8). Two proteins have been identified as key components of SOCE: STIM1 (stromal interaction molecule 1), which senses ER Ca2+ store content and translocates to the plasma membrane upon store depletion, where it then activates Orai1, the pore-forming component of the CRAC (Ca2+ release-activated Ca2+) channel. Previous studies reported that co-expression of STIM1 and Orai1 in HEK-293 (human embryonic kidney 293) cells enhances Ca2+ -stimulated AC8 activity and that AC8 and Orai1 directly interact to enhance this regulation. Nonetheless, the additional involvement of TRPC (transient receptor potential canonical) channels in SOCE has also been proposed. In the present study, we evaluate the contribution of TRPC1 to SOCE-mediated regulation of Ca2+ -sensitive ACs in HEK-293 cells stably expressing AC8 (HEK-AC8) and HSG (human submandibular gland) cells expressing an endogenous Ca2+ -inhibited AC6. We demonstrate a role for TRPC1 as an integral component of SOCE, alongside STIM1 and Orai1, in regulating Ca2+ fluxes within AC microdomains and influencing cAMP production.