Different binding property of STIM1 and its novel splice variant STIM1L to Orai1, TRPC3, and TRPC6 channels
Different binding property of STIM1 and its novel splice variant STIM1L to Orai1, TRPC3, and TRPC6 channels
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DOI：
10.1016/j.bbrc.2012.10.034
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发表时间：
2012-11-16
影响因子：
3.1
通讯作者：
Miwa, Soichi
中科院分区：
文献类型：
--
作者：
Horinouchi, Takahiro;Higashi, Tsunehito;Miwa, Soichi
基质相互作用分子1（Stromal interaction molecule 1，STIM 1）是内质网（endoplasmic reticulum，ER）中的钙离子传感器，调控ER内钙离子水平。最近的一项研究表明，STIM 1 L，一种新的剪接变体STIM 1，在啮齿动物和人类骨骼肌的各种组织中表达，并且STIM 1 L与肌动蛋白丝的相互作用允许通过Orai 1通道介导的钙库操纵的钙离子内流（SOCE）的快速激活。在这里，我们描述了人STIM 1和STIM 1 L的mRNA表达和功能，并比较了它们与作为钙池操纵的钙通道（SOCC）的Orai 1以及作为内皮素A型受体（ETAR）操纵的钙通道（ROCC）的TRPC 3（瞬时受体电位典型3）和TRPC 6通道的结合特性。尽管STIM 1的mRNA在人体组织中普遍表达，但STIM 1 L仅在骨骼肌中检测到。在稳定表达ETAR的人胚肾293细胞中，STIM 1 L增强毒胡萝卜素和内皮素-1诱导的SOCE比STIM 1更强，然而，它倾向于通过TRPC 3和TRPC 6更强地抑制ETAR操作的Ca 2+内流（ROCE）。免疫共沉淀实验表明，与STIM 1相比，STIM 1 L更丰富地结合Orai 1以及TRPC 3和TRPC 6。这些结果表明，ST 1 M1L与SOCCs和ROCCs的较高结合能力在Ca 2+信号转导的调节中起重要作用，例如通过rail增强SOCE和通过TRPC 3和TRPC 6抑制ROCE。(C)2012 Elsevier Inc. All rights reserved.
Stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca2+ sensor to control ER Ca2+ levels. A recent study has shown that STIM1L, a new splice variant of STIM1, is expressed in various tissues of rodent and in human skeletal muscle, and that the interaction of STIM1L with actin filament allows rapid activation of store-operated Ca2+ entry (SOCE) mediated through Orai1 channels. Here, we characterize mRNA expression and function of human STIM1 and STIM1L, and compare their binding property to Orai1 functioning as store-operated Ca2+ channels (SOCCs), and TRPC3 (transient receptor potential canonical 3) and TRPC6 channels functioning as endothelin type A receptor (ETAR)-operated Ca2+ channels (ROCCs). Although mRNA for STIM1 was ubiquitously expressed in human tissues, STIM1L was detected only in skeletal muscle. STIM1L augmented thapsigargin- and endothelin-1 -induced SOCE more strongly than STIM1 in human embryonic kidney 293 cells stably expressing ETAR, whereas, it tends to suppress ETAR-operated Ca2+ entry (ROCE) via TRPC3 and TRPC6 more strongly than STIM1. Coimmunoprecipitation experiments have revealed that when compared with STIM1, STIM1L binds more abundantly to Orai1 and also to TRPC3 and TRPC6. These results suggest that the higher binding capacity of ST1M1L to SOCCs and ROCCs plays an important role in the regulation of Ca2+ signaling such as the augmentation of SOCE via rail and the inhibition of ROCE via TRPC3 and TRPC6. (C) 2012 Elsevier Inc. All rights reserved.