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Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome.

ABSTRACT: Voltage-gated K(+) channels control excitability in neuronal and various other tissues. We identified three unique alpha-subunits of voltage-gated K(+)-channels in the human genome. Analysis of the full-length sequences indicated that one represents a previously uncharacterized member of the Kv6 subfamily, Kv6.3, whereas the others are the first members of two unique subfamilies, Kv10.1 and Kv11.1. Although they have all of the hallmarks of voltage-gated K(+) channel subunits, they did not produce K(+) currents when expressed in mammalian cells. Confocal microscopy showed that Kv6.3, Kv10.1, and Kv11.1 alone did not reach the plasma membrane, but were retained in the endoplasmic reticulum. Yeast two-hybrid experiments failed to show homotetrameric interactions, but showed interactions with Kv2.1, Kv3.1, and Kv5.1. Co-expression of each of the previously uncharacterized subunits with Kv2.1 resulted in plasma membrane localization with currents that differed from typical Kv2.1 currents. This heteromerization was confirmed by co-immunoprecipitation. The Kv2 subfamily consists of only two members and uses interaction with "silent subunits" to diversify its function. Including the subunits described here, the "silent subunits" represent one-third of all Kv subunits, suggesting that obligatory heterotetramer formation is more widespread than previously thought.

SUBMITTER: Ottschytsch N

PROVIDER: S-EPMC123007 | biostudies-literature | 2002 Jun

REPOSITORIES: biostudies-literature

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Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome.

Ottschytsch N N Raes A A Van Hoorick D D Snyders D J DJ

Proceedings of the National Academy of Sciences of the United States of America 20020601 12

Voltage-gated K(+) channels control excitability in neuronal and various other tissues. We identified three unique alpha-subunits of voltage-gated K(+)-channels in the human genome. Analysis of the full-length sequences indicated that one represents a previously uncharacterized member of the Kv6 subfamily, Kv6.3, whereas the others are the first members of two unique subfamilies, Kv10.1 and Kv11.1. Although they have all of the hallmarks of voltage-gated K(+) channel subunits, they did not produ ...[more]

PMID: 12060745

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Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome.

Publications

Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome.

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