The sigma-1 receptor chaperone as an inter-organelle signaling modulator.
Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intramitochondrial calcium (Ca(2+)) homeostasis and cellular bioenergetics. ER-nucleus signaling attenuates ER stress. ER-plasma membrane signaling regulates cytosolic Ca(2+) 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 ER-nucleus crosstalk. 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 might relate to this unique action of Sig-1Rs.
Su
Tsung-Ping
TP
Cellular Pathobiology Section, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, suite 3304, 333 Cassell Drive, Baltimore, MD 21224, USA. TSU@intra.nida.nih.gov
Hayashi
Teruo
T
Maurice
Tangui
T
Buch
Shilpa
S
Ruoho
Arnold E
AE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D015394:Molecular Structure; D021381:Protein Transport / Q000502:physiology; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000097605:Sigma-1 Receptor
D002118:Calcium; D008024:Ligands; D018832:Molecular Chaperones; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor