RGD Reference Report - Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes. - Rat Genome Database

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Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes.

Authors: El-Haou, S  Balse, E  Neyroud, N  Dilanian, G  Gavillet, B  Abriel, H  Coulombe, A  Jeromin, A  Hatem, SN 
Citation: El-Haou S, etal., Circ Res. 2009 Mar 27;104(6):758-69. Epub 2009 Feb 12.
RGD ID: 2306822
Pubmed: PMID:19213956   (View Abstract at PubMed)
DOI: DOI:10.1161/CIRCRESAHA.108.191007   (Journal Full-text)

Membrane-associated guanylate kinase (MAGUK) proteins are major determinants of the organization of ion channels in the plasma membrane in various cell types. Here, we investigated the interaction between the MAGUK protein SAP97 and cardiac Kv4.2/3 channels, which account for a large part of the outward potassium current, I(to), in heart. We found that the Kv4.2 and Kv4.3 channels C termini interacted with SAP97 via a SAL amino acid sequence. SAP97 and Kv4.3 channels were colocalized in the sarcolemma of cardiomyocytes. In CHO cells, SAP97 clustered Kv4.3 channels in the plasma membrane and increased the current independently of the presence of KChIP and dipeptidyl peptidase-like protein-6. Suppression of SAP97 by using short hairpin RNA inhibited I(to) in cardiac myocytes, whereas its overexpression by using an adenovirus increased I(to). Kv4.3 channels without the SAL sequence were no longer regulated by Ca2+/calmodulin kinase (CaMK)II inhibitors. In cardiac myocytes, pull-down and coimmunoprecipitation assays showed that the Kv4 channel C terminus, SAP97, and CaMKII interact together, an interaction suppressed by SAP97 silencing and enhanced by SAP97 overexpression. In HEK293 cells, SAP97 silencing reproduced the effects of CaMKII inhibition on current kinetics and suppressed Kv4/CaMKII interactions. In conclusion, SAP97 is a major partner for surface expression and CaMKII-dependent regulation of cardiac Kv4 channels.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of potassium ion transport  IMP 2306822 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transmembrane transporter binding  IPIKcnd2 (Rattus norvegicus) and Kcnd3 (Rattus norvegicus)2306822protein C-terminus SAL motif bindingRGD 

Objects Annotated

Genes (Rattus norvegicus)
Dlg1  (discs large MAGUK scaffold protein 1)


Additional Information