Store-operated cyclic AMP signalling mediated by STIM1
Store-operated cyclic AMP signalling mediated by STIM1
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DOI：
10.1038/ncb1850
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发表时间：
2009-04-01
影响因子：
21.3
通讯作者：
Hofer, Aldebaran M.
中科院分区：
文献类型：
--
作者：
Lefkimmiatis, Konstantinos;Srikanthan, Meera;Hofer, Aldebaran M.
内质网（ER）中Ca 2+的耗竭导致质膜Ca 2+进入通道的激活。这种“存储操作”的过程需要跨膜ER Ca2+传感器蛋白，基质相互作用分子1（STIM 1），在细胞表面的Ca2+通道紧密并列的网站易位。然而，目前还不知道是否减少钙+商店耦合到其他信号通路通过这种机制。我们发现，降低游离Ca2+在ER中的浓度，独立于胞浆Ca2+浓度，也导致腺苷酸环化酶的招聘。这导致增强的cAMP积累和PKA激活，使用基于FRET的cAMP指标测量。STIM 1的易位是有效耦合ER Ca 2+耗竭腺苷酸环化酶活性所必需的。我们提出存在一种途径（存储操作的cAMP信号或SOcAMPS），其中内部Ca2+存储的内容通过涉及STIM 1的过程直接连接到cAMP信号。
Depletion of Ca2+ from the endoplasmic reticulum ( ER) results in activation of plasma membrane Ca2+ entry channels. This 'store-operated' process requires translocation of a transmembrane ER Ca2+ sensor protein, stromal interaction molecule 1 (STIM1), to sites closely apposed to Ca2+ channels at the cell surface. However, it is not known whether a reduction in Ca2+ stores is coupled to other signalling pathways by this mechanism. We found that lowering the concentration of free Ca2+ in the ER, independently of the cytosolic Ca2+ concentration, also led to recruitment of adenylyl cyclases. This resulted in enhanced cAMP accumulation and PKA activation, measured using FRET-based cAMP indicators. Translocation of STIM1 was required for efficient coupling of ER Ca2+ depletion to adenylyl cyclase activity. We propose the existence of a pathway (store-operated cAMP signalling or SOcAMPS) in which the content of internal Ca2+ stores is directly connected to cAMP signalling through a process that involves STIM1.