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

Tsung Ping Su, Teruo Hayashi, Tangui Maurice, Shilpa Buch, Arnold E. Ruoho

Research output: Contribution to journalShort surveypeer-review

304 Scopus citations


Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intramitochondrial 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 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.

Original languageEnglish (US)
Pages (from-to)557-566
Number of pages10
JournalTrends in Pharmacological Sciences
Issue number12
StatePublished - Dec 2010

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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