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A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels.

Authors: Shibata, R  Misonou, H  Campomanes, CR  Anderson, AE  Schrader, LA  Doliveira, LC  Carroll, KI  Sweatt, JD  Rhodes, KJ  Trimmer, JS 
Citation: Shibata R, etal., J Biol Chem 2003 Sep 19;278(38):36445-54. Epub 2003 Jun 26.
Pubmed: (View Article at PubMed) PMID:12829703
DOI: Full-text: DOI:10.1074/jbc.M306142200

Kv4 potassium channels regulate action potentials in neurons and cardiac myocytes. Co-expression of EF hand-containing Ca2+-binding proteins termed KChIPs with pore-forming Kv4 alpha subunits causes changes in the gating and amplitude of Kv4 currents (An, W. F., Bowlby, M. R., Betty, M., Cao, J., Ling, H. P., Mendoza, G., Hinson, J. W., Mattsson, K. I., Strassle, B. W., Trimmer, J. S., and Rhodes, K. J. (2000) Nature 403, 553-556). Here we show that KChIPs profoundly affect the intracellular trafficking and molecular properties of Kv4.2 alpha subunits. Co-expression of KChIPs1-3 causes a dramatic redistribution of Kv4.2, releasing intrinsic endoplasmic reticulum retention and allowing for trafficking to the cell surface. KChIP co-expression also causes fundamental changes in Kv4.2 steady-state expression levels, phosphorylation, detergent solubility, and stability that reconstitute the molecular properties of Kv4.2 in native cells. Interestingly, the KChIP4a isoform, which exhibits unique effects on Kv4 channel gating, does not exert these effects on Kv4.2 and negatively influences the impact of other KChIPs. We provide evidence that these KChIP effects occur through the masking of an N-terminal Kv4.2 hydrophobic domain. These studies point to an essential role for KChIPs in determining both the biophysical and molecular characteristics of Kv4 channels and provide a molecular basis for the dramatic phenotype of KChIP knockout mice.

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CRRD Object Information
CRRD ID: 1299235
Created: 2004-06-01
Species: All species
Last Modified: 2006-04-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.