Amplification of CRAC current by STIM1 and CRACM1 (Orai1)

Amplification of CRAC current by STIM1 and CRACM1 (Orai1)
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DOI:
10.1038/ncb1435
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发表时间:
2006-07-01
影响因子:
21.3
通讯作者:
Kinet, Jean-Pierre
Kinet, Jean-Pierre
中科院分区:
生物学1区
文献类型:
--
作者:
Peinelt, Christine;Vig, Monika;Kinet, Jean-Pierre

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在许多细胞中,细胞内钙储存的消耗激活了储存操作的钙通过质膜进入。内质网中假定的钙传感器STIM1和质膜中的钙释放活化钙(CRAC)调节剂CRACM1(也称为Orai1)最近被证明对控制储存操作的CRAC电流(I-CRAC)至关重要(1-4)。然而,任何一种蛋白的个体过表达都不能显著扩增I-CRAC。在这里,我们展示了STIM1和CRACM1在功能上相互作用。这两种蛋白的过表达大大增强了I-CRAC,表明STIM1和CRACM1相互限制存储操作电流,CRACM1可能是长期寻找的CRAC通道。
Depletion of intracellular calcium stores activates store-operated calcium entry across the plasma membrane in many cells. STIM1, the putative calcium sensor in the endoplasmic reticulum, and the calcium release-activated calcium ( CRAC) modulator CRACM1 ( also known as Orai1) in the plasma membrane have recently been shown to be essential for controlling the store-operated CRAC current ( I-CRAC)(1-4). However, individual overexpression of either protein fails to significantly amplify I-CRAC. Here, we show that STIM1 and CRACM1 interact functionally. Overexpression of both proteins greatly potentiates I-CRAC, suggesting that STIM1 and CRACM1 mutually limit store-operated currents and that CRACM1 may be the long-sought CRAC channel.