RGD Reference Report - Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)-associated proteins. - Rat Genome Database

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Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)-associated proteins.

Authors: Leonoudakis, D  Conti, LR  Anderson, S  Radeke, CM  McGuire, LM  Adams, ME  Froehner, SC  Yates JR, 3RD  Vandenberg, CA 
Citation: Leonoudakis D, etal., J Biol Chem. 2004 May 21;279(21):22331-46. Epub 2004 Mar 15.
RGD ID: 1581350
Pubmed: PMID:15024025   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M400285200   (Journal Full-text)

Inward rectifier potassium (Kir) channels play important roles in the maintenance and control of cell excitability. Both intracellular trafficking and modulation of Kir channel activity are regulated by protein-protein interactions. We adopted a proteomics approach to identify proteins associated with Kir2 channels via the channel C-terminal PDZ binding motif. Detergent-solubilized rat brain and heart extracts were subjected to affinity chromatography using a Kir2.2 C-terminal matrix to purify channel-interacting proteins. Proteins were identified with multidimensional high pressure liquid chromatography coupled with electrospray ionization tandem mass spectrometry, N-terminal microsequencing, and immunoblotting with specific antibodies. We identified eight members of the MAGUK family of proteins (SAP97, PSD-95, Chapsyn-110, SAP102, CASK, Dlg2, Dlg3, and Pals2), two isoforms of Veli (Veli-1 and Veli-3), Mint1, and actin-binding LIM protein (abLIM) as Kir2.2-associated brain proteins. From heart extract purifications, SAP97, CASK, Veli-3, and Mint1 also were found to associate with Kir2 channels. Furthermore, we demonstrate for the first time that components of the dystrophin-associated protein complex, including alpha1-, beta1-, and beta2-syntrophin, dystrophin, and dystrobrevin, interact with Kir2 channels, as demonstrated by immunoaffinity purification and affinity chromatography from skeletal and cardiac muscle and brain. Affinity pull-down experiments revealed that Kir2.1, Kir2.2, Kir2.3, and Kir4.1 all bind to scaffolding proteins but with different affinities for the dystrophin-associated protein complex and SAP97, CASK, and Veli. Immunofluorescent localization studies demonstrated that Kir2.2 co-localizes with syntrophin, dystrophin, and dystrobrevin at skeletal muscle neuromuscular junctions. These results suggest that Kir2 channels associate with protein complexes that may be important to target and traffic channels to specific subcellular locations, as well as anchor and stabilize channels in the plasma membrane.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
PDZ domain binding  IPIKcnj12 (Rattus norvegicus)1581350; 1581350; 1581350; 1581350; 1581350; 1581350; 1581350; 1581350; 1581350; 1581350; 1581350; 1581350; 1581350; 1581350 RGD 
PDZ domain binding  IPIKCNJ4 (Homo sapiens)1581350; 1581350; 1581350; 1581350; 1581350 RGD 
PDZ domain binding  IPIKcnj2 (Mus musculus)1581350; 1581350; 1581350; 1581350; 1581350 RGD 
PDZ domain binding  IPIKcnj10 (Rattus norvegicus)1581350; 1581350 RGD 
protein binding  IPIKcnj12 (Rattus norvegicus)1581350 RGD 
protein binding  IPISnta1 (Rattus norvegicus)1581350; 1581350 RGD 
protein binding  IPIDmd (Rattus norvegicus)1581350; 1581350 RGD 
protein binding  IPIDlg4 (Rattus norvegicus)1581350 RGD 
protein binding  IPIDlg3 (Rattus norvegicus)1581350 RGD 
protein binding  IPILin7a (Rattus norvegicus)1581350 RGD 
protein binding  IPILin7c (Rattus norvegicus)1581350 RGD 
protein binding  IPIApba1 (Rattus norvegicus)1581350 RGD 
protein binding  IPICask (Rattus norvegicus)1581350 RGD 
protein binding  IPIMpp3 (Rattus norvegicus)1581350 RGD 
protein binding  IPIMpp2 (Rattus norvegicus)1581350 RGD 
protein binding  IPIDlg2 (Rattus norvegicus)1581350 RGD 
protein binding  IPIDlg1 (Rattus norvegicus)1581350 RGD 
protein binding  IPIAblim1 (Rattus norvegicus)1581350 RGD 
protein binding  IPIDtna (Rattus norvegicus)1581350 RGD 
protein binding  IPIPals2 (Rattus norvegicus)1581350 RGD 
protein binding  IPISntb2_predicted (Rattus norvegicus)1581350 RGD 
protein binding  IPISntb1 (Rattus norvegicus)1581350 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ablim1  (actin-binding LIM protein 1)
Apba1  (amyloid beta precursor protein binding family A member 1)
Cask  (calcium/calmodulin dependent serine protein kinase)
Dlg1  (discs large MAGUK scaffold protein 1)
Dlg2  (discs large MAGUK scaffold protein 2)
Dlg3  (discs large MAGUK scaffold protein 3)
Dlg4  (discs large MAGUK scaffold protein 4)
Dmd  (dystrophin)
Dtna  (dystrobrevin, alpha)
Kcnj10  (potassium inwardly-rectifying channel, subfamily J, member 10)
Kcnj12  (potassium inwardly-rectifying channel, subfamily J, member 12)
Lin7a  (lin-7 homolog A, crumbs cell polarity complex component)
Lin7c  (lin-7 homolog C, crumbs cell polarity complex component)
Mpp2  (MAGUK p55 scaffold protein 2)
Mpp3  (MAGUK p55 scaffold protein 3)
Snta1  (syntrophin, alpha 1)
Sntb1  (syntrophin, beta 1)

Objects referenced in this article
Gene Pals2 protein associated with LIN7 2, MAGUK p55 family member Rattus norvegicus

Additional Information