RGD Reference Report - Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. - Rat Genome Database

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Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.

Authors: Hayashi, T  Su, TP 
Citation: Hayashi T and Su TP, Cell. 2007 Nov 2;131(3):596-610.
RGD ID: 8554014
Pubmed: PMID:17981125   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cell.2007.08.036   (Journal Full-text)

Communication between the endoplasmic reticulum (ER) and mitochondrion is important for bioenergetics and cellular survival. The ER supplies Ca(2+) directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). We found here that the ER protein sigma-1 receptor (Sig-1R), which is implicated in neuroprotection, carcinogenesis, and neuroplasticity, is a Ca(2+)-sensitive and ligand-operated receptor chaperone at MAM. Normally, Sig-1Rs form a complex at MAM with another chaperone, BiP. Upon ER Ca(2+) depletion or via ligand stimulation, Sig-1Rs dissociate from BiP, leading to a prolonged Ca(2+) signaling into mitochondria via IP3Rs. Sig-1Rs can translocate under chronic ER stress. Increasing Sig-1Rs in cells counteracts ER stress response, whereas decreasing them enhances apoptosis. These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q9R0C98554014PMID:17981125IntAct 
protein binding enablesIPIUniProtKB:P067618554014PMID:17981125IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Hspa5  (heat shock protein family A (Hsp70) member 5)
Sigmar1  (sigma non-opioid intracellular receptor 1)


Additional Information