RGD Reference Report - Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and behavioral responses to cocaine. - Rat Genome Database

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Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and behavioral responses to cocaine.

Authors: Kourrich, S  Hayashi, T  Chuang, JY  Tsai, SY  Su, TP  Bonci, A 
Citation: Kourrich S, etal., Cell. 2013 Jan 17;152(1-2):236-47. doi: 10.1016/j.cell.2012.12.004.
RGD ID: 8554497
Pubmed: PMID:23332758   (View Abstract at PubMed)
PMCID: PMC4159768   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2012.12.004   (Journal Full-text)

The sigma-1 receptor (Sig-1R), an endoplasmic reticulum (ER) chaperone protein, is an interorganelle signaling modulator that potentially plays a role in drug-seeking behaviors. However, the brain site of action and underlying cellular mechanisms remain unidentified. We found that cocaine exposure triggers a Sig-1R-dependent upregulation of D-type K(+) current in the nucleus accumbens (NAc) that results in neuronal hypoactivity and thereby enhances behavioral cocaine response. Combining ex vivo and in vitro studies, we demonstrated that this neuroadaptation is caused by a persistent protein-protein association between Sig-1Rs and Kv1.2 channels, a phenomenon that is associated to a redistribution of both proteins from intracellular compartments to the plasma membrane. In conclusion, the dynamic Sig-1R-Kv1.2 complex represents a mechanism that shapes neuronal and behavioral response to cocaine. Functional consequences of Sig-1R binding to K(+) channels may have implications for other chronic diseases where maladaptive intrinsic plasticity and Sig-1Rs are engaged.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P631418554497PMID:23332758IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Sigmar1  (sigma non-opioid intracellular receptor 1)


Additional Information