Feliciangeli, Sylvain and Tardy, Magalie P. and Sandoz, Guillaume and Chatelain, Franck C. and Warth, Richard and Barhanin, Jacques and Bendahhou, Said and Lesage, Florian (2010) Potassium Channel Silencing by Constitutive Endocytosis and Intracellular Sequestration. JOURNAL OF BIOLOGICAL CHEMISTRY, 285 (7). pp. 4798-4805. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
Tandem of P domains in a weak inwardly rectifying K+ channel 1 (TWIK1) is a K+ channel that produces unusually low levels of current. Replacement of lysine 274 by a glutamic acid (K274E) is associated with stronger currents. This mutation would prevent conjugation of a small ubiquitin modifier peptide to Lys-274, a mechanism proposed to be responsible for channel silencing. However, we found no biochemical evidence of TWIK1 sumoylation, and we showed that the conservative change K274R did not increase current, suggesting that K274E modifies TWIK1 gating through a charge effect. Now we rule out an eventual effect of K274E on TWIK1 trafficking, and we provide convincing evidence that TWIK1 silencing results from its rapid retrieval from the cell surface. TWIK1 is internalized via a dynamin-dependent mechanism and addressed to the recycling endosomal compartment. Mutation of a diisoleucine repeat located in its cytoplasmic C terminus (I293A, I294A) stabilizes TWIK1 at the plasma membrane, resulting in robust currents. The effects of I293A, I294A on channel trafficking and of K274E on channel activity are cumulative, promoting even more currents. Activation of serotoninergic receptor 5-HT1R or adrenoreceptor alpha 2A-AR stimulates TWIK1 but has no effect on TWIK1I293A, I294A, suggesting that G(i) protein activation is a physiological signal for increasing the number of active channels at the plasma membrane.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DOMAIN K+ CHANNELS; MEMBRANE; CELLS; ENDOSOMES; DYNAMIN; TREK-1; LOCALIZATION; PHARMACOLOGY; CONDUCTANCE; MODULATION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Aug 2020 07:12 |
| Last Modified: | 06 Aug 2020 07:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25153 |
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