Co-assembly of Kv4 α subunits with K+ channel-interacting protein 2 stabilizes protein expression and promotes surface retention of channel complexes

Nicholas C. Foeger, Céline Marionneau, Jeanne M. Nerbonne

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Members of the K+ channel-interacting protein (KChIP) family bind the distal N termini of members of the Shal subfamily of voltage-gated K+ channel (Kv4) pore-forming (α) subunits to generate rapidly activating, rapidly inactivating neuronal Atype (IA) and cardiac transient outward (Ito) currents. In heterologous cells, KChIP co-expression increases cell surface expression of Kv4 α subunits and Kv4 current densities, findings interpreted to suggest that Kv4·KChIP complex formation enhances forward trafficking of channels (from the endoplasmic reticulum or the Golgi complex) to the surface membrane. The results of experiments here, however, demonstrate that KChIP2 increases cell surface Kv4.2 protein expression (∼40-fold) by an order of magnitude more than the increase in total protein (∼2-fold) or in current densities (∼3-fold), suggesting that mechanisms at the cell surface regulate the functional expression of Kv4.2 channels. Additional experiments demonstrated that KChIP2 decreases the turnover rate of cell surface Kv4.2 protein by inhibiting endocytosis and/or promoting recycling. Unexpectedly, the experiments here also revealed that Kv4.2·KChIP2 complex formation stabilizes not only (total and cell surface) Kv4.2 but also KChIP2 protein expression. This reciprocal protein stabilization and Kv4·KChIP2 complex formation are lost with deletion of the distal (10 amino acids) Kv4.2 N terminus. Taken together, these observations demonstrate that KChIP2 differentially regulates total and cell surface Kv4.2 protein expression and Kv4 current densities.

Original languageEnglish
Pages (from-to)33413-33422
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number43
DOIs
StatePublished - Oct 22 2010

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