Tsai Shang-Yi, Hayashi Teruo, Mori Tomohisa, Su Tsung-Ping
Cellular Pathobiology Section, Cellular Neurobiology Research Branch, IRP, NIDA, NIH, DHHS, 333 Cassell Drive, Baltimore, MD 21224, USA.
Cent Nerv Syst Agents Med Chem. 2009 Sep;9(3):184-9. doi: 10.2174/1871524910909030184.
Chaperones are proteins that assist the correct folding of other protein clients either when the clients are being synthesized or at their functional localities. Chaperones are responsible for certain diseases. The sigma-1 receptor is recently identified as a receptor chaperone whose activity can be activated/deactivated by specific ligands. Under physiological conditions, the sigma-1 receptor chaperones the functional IP3 receptor at the endoplasmic reticulum and mitochondrion interface to ensure proper Ca(2+) signaling from endoplasmic reticulum into mitochondrion. However, under pathological conditions whereby cells encounter enormous stress that results in the endoplasmic reticulum losing its global Ca(2+) homeostasis, the sigma-1 receptor translocates and counteracts the arising apoptosis. Thus, the sigma-1 receptor is a receptor chaperone essential for the metabotropic receptor signaling and for the survival against cellular stress. The sigma-1 receptor has been implicated in many diseases including addiction, pain, depression, stroke, and cancer. Whether the chaperone activity of the sigma-1 receptor attributes to those diseases awaits further investigation.
伴侣蛋白是一类蛋白质，它们在其他蛋白质底物合成时或在其功能位点协助这些底物正确折叠。伴侣蛋白与某些疾病的发生有关。σ-1受体最近被鉴定为一种受体伴侣蛋白，其活性可被特定配体激活或失活。在生理条件下，σ-1受体在内质网和线粒体界面陪伴功能性肌醇-1,4,5-三磷酸（IP3）受体，以确保内质网到线粒体的钙（Ca2+）信号传导正常。然而，在病理条件下，细胞遭遇巨大应激导致内质网失去整体钙稳态时，σ-1受体易位并对抗由此引发的细胞凋亡。因此，σ-1受体是一种受体伴侣蛋白，对代谢型受体信号传导以及细胞抵抗应激存活至关重要。σ-1受体与许多疾病有关，包括成瘾、疼痛、抑郁、中风和癌症。σ-1受体的伴侣蛋白活性是否与这些疾病有关，还有待进一步研究。
