RGD Reference Report - The endoplasmic reticulum Ca2+-pump SERCA2b interacts with G protein-coupled receptors and enhances their expression at the cell surface. - Rat Genome Database

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The endoplasmic reticulum Ca2+-pump SERCA2b interacts with G protein-coupled receptors and enhances their expression at the cell surface.

Authors: Tuusa, JT  Markkanen, PM  Apaja, PM  Hakalahti, AE  Petaja-Repo, UE 
Citation: Tuusa JT, etal., J Mol Biol. 2007 Aug 17;371(3):622-38. Epub 2007 Mar 15.
RGD ID: 2292598
Pubmed: PMID:17588601   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jmb.2007.02.108   (Journal Full-text)

Calcium (Ca(2+)) plays a pivotal role in both cellular signaling and protein synthesis. However, it is not well understood how calcium metabolism and synthesis of secreted and membrane-bound proteins are related. Here we demonstrate that the sarco(endo)plasmic reticulum Ca(2+) ATPase 2b (SERCA2b), which maintains high Ca(2+) concentration in the lumen of the endoplasmic reticulum, interacts specifically with the human delta opioid receptor during early steps of receptor biogenesis in human embryonic kidney 293 cells. The interaction involves newly synthesized incompletely folded receptor precursors, because the association between the delta opioid receptor and SERCA2b (i) was short-lived and took place soon after receptor translation, (ii) was not affected by misfolding of the receptor, and (iii) decreased if receptor folding was enhanced by opioid receptor pharmacological chaperone. The physical association with SERCA2b was found to be a universal feature among G protein-coupled receptors within family A and was shown to occur also between the endogenously expressed luteinizing hormone receptor and SERCA2b in rat ovaries. Importantly, active SERCA2b rather than undisturbed Ca(2+) homeostasis was found to be essential for delta opioid receptor biogenesis, as inhibition of its Ca(2+) pumping activity by thapsigargin reduced the interaction and impaired the efficiency of receptor maturation, two phenomena that were not affected by a Ca(2+) ionophore A23187. Nevertheless, inhibition of SERCA2b did not compromise the functionality of receptors that were able to mature. Thus, we propose that the association with SERCA2b is required for efficient folding and/or membrane integration of G protein-coupled receptors.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ATPase binding  IPIAtp2a2 (Rattus norvegicus)2292598during receptor processing in ERRGD 
lutropin-choriogonadotropic hormone receptor binding  IPILhcgr (Rattus norvegicus)2292598during receptor processing in ERRGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp2a2  (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2)
Lhcgr  (luteinizing hormone/choriogonadotropin receptor)


Additional Information