RGD Reference Report - Identification of an endogenous inhibitor of the cardiac Na+/Ca2+ exchanger, phospholemman. - Rat Genome Database

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Identification of an endogenous inhibitor of the cardiac Na+/Ca2+ exchanger, phospholemman.

Authors: Ahlers, BA  Zhang, XQ  Moorman, JR  Rothblum, LI  Carl, LL  Song, J  Wang, J  Geddis, LM  Tucker, AL  Mounsey, JP  Cheung, JY 
Citation: Ahlers BA, etal., J Biol Chem. 2005 May 20;280(20):19875-82. Epub 2005 Mar 17.
RGD ID: 1581354
Pubmed: PMID:15774479   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M414703200   (Journal Full-text)

Rapid and precise control of Na(+)/Ca(2+) exchanger (NCX1) activity is essential in the maintenance of beat-to-beat Ca(2+) homeostasis in cardiac myocytes. Here, we show that phospholemman (PLM), a 15-kDa integral sarcolemmal phosphoprotein, is a novel endogenous protein inhibitor of cardiac NCX1. Using a heterologous expression system that is devoid of both endogenous PLM and NCX1, we first demonstrated by confocal immunofluorescence studies that both exogenous PLM and NCX1 co-localized at the plasma membrane. Reciprocal co-immunoprecipitation studies revealed specific protein-protein interaction between PLM and NCX1. The functional consequences of direct association of PLM with NCX1 was the inhibition of NCX1 activity, as demonstrated by whole-cell patch clamp studies to measure NCX1 current density and radiotracer flux assays to assess Na(+)-dependent (45)Ca(2+) uptake. Inhibition of NCX1 by PLM was specific, because a single mutation of serine 68 to alanine in PLM resulted in a complete loss of inhibition of NCX1 current, although association of the PLM mutant with NCX1 was unaltered. In native adult cardiac myocytes, PLM co-immunoprecipitated with NCX1. We conclude that PLM, a member of the FXYD family of small ion transport regulators known to modulate Na(+)-K(+)-ATPase, also regulates Na(+)/Ca(2+) exchange in the heart.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of calcium ion transport  IMP 1581354 RGD 
regulation of sodium ion transport  IMP 1581354 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Fxyd1  (FXYD domain-containing ion transport regulator 1)
Slc8a1  (solute carrier family 8 member A1)


Additional Information