The sigma-1 receptor chaperone as an inter-organelle signaling modulator.

The sigma-1 receptor chaperone as an inter-organelle signaling modulator.
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DOI:
10.1016/j.tips.2010.08.007
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发表时间:
2010-12
影响因子:
13.8
通讯作者:
Ruoho AE
Ruoho AE
中科院分区:
医学1区
文献类型:
--
作者:
Su TP;Hayashi T;Maurice T;Buch S;Ruoho AE

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细胞器间信号传导在许多生理功能中起着重要作用。内质网(ER)-钙通道信号影响线粒体内钙(Ca 2+)稳态和细胞生物能量学。ER核信号传导减弱ER应激。ER-质膜信号调节胞质Ca 2+稳态,ER-质膜上信号调节海马树突棘形成。在这里,我们提出,σ-1受体(Sig-1R),ER伴侣蛋白,作为一个细胞器间的信号转导调制器。Sig-1R通常位于称为MAM(ER-配体相关ER膜)的ER-配体接触处,其中Sig-1R调节ER-配体信号传导和ER-核串扰。当细胞受到配体刺激或经历长时间应激时,Sig-1Rs从MAM易位到ER网状网络和质膜/质膜以调节多种功能蛋白,包括离子通道、受体和激酶。因此,Sig-1R在MAM局部和质膜/质膜远程充当细胞器间信号传导调节剂。Sig-1Rs的许多药理学/生理学作用可能与Sig-1Rs的这种独特作用有关。
Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intra-mitochondrial calcium (Ca2+) homeostasis and cellular bioenergetics. ER-nucleus signaling attenuates ER stress. ER-plasma membrane signaling regulates cytosolic Ca2+ homeostasis, and ER-mitochondrion-plasma membrane signaling regulates hippocampal dendritic spine formation. Here we propose that the sigma-1 receptor (Sig-1R), an ER chaperone protein, acts as an inter-organelle signaling modulator. Sig-1Rs normally reside at the ER-mitochondrion contact called the MAM (mitochondrion-associated ER membrane), where Sig-1Rs regulate ER-mitochondrion signaling and the ER-nucleus cross-talk. When cells are stimulated by ligands or undergo prolonged stress, Sig-1Rs translocate from the MAM to the ER reticular network and plasmalemma/plasma membrane to regulate a variety of functional proteins, including ion channels, receptors, and kinases. Thus, the Sig-1R serves as an inter-organelle signaling modulator locally at the MAM and remotely at the plasmalemma/plasma membrane. Many pharmacological/physiological effects of Sig-1Rs may relate to this unique action of Sig-1Rs.
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