Membrane Trafficking Controls K2P1/TWIK1 Channel Expression at the Cell Surface
| Autor: | Markus Reichold, Richard Warth, Guillaume Sandoz, Sylvain Feliciangeli, Florian Lesage, Magalie P. Tardy, Saïd Bendahhou, Franck C. Chatelain, Jacques Barhanin |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0303 health sciences
Cell type Endosome Cell SUMO protein Xenopus Biophysics Biology biology.organism_classification Endocytosis Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure medicine Heterologous expression 030217 neurology & neurosurgery Intracellular 030304 developmental biology |
| Zdroj: | Biophysical Journal. (3):537a |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2009.12.2914 |
| Popis: | Two-P-domain potassium (K2P) channels produce background conductances involved in neuronal excitability and cell volume regulation. In contrast with other K2P channels, little is known about TWIK1 (K2P1), despite the fact that it has been the first K2P channel cloned and expressed (Lesage et al, EMBO J. 1996, 15, 1004-1011). Functional studies on TWIK1 have been impeded by the fact that it produces only modest current upon heterologous expression in Xenopus oocytes, and that so far, no currents similar to TWIK1 have been reported in native cells. It has been proposed that K2P1 was present at the cell surface but silenced by conjugation of a SUMO peptide to an unconventional sumoylation site (Rajan et al, Cell. 2005, 121, 37-47). However, we did not observe any quantitative sumoylation of TWIK1 in vivo or even in vitro. Also, we have shown that inactivation of the putative sumoylation by a conservative lys to arg mutation was without effect on the level of TWIK1 current (Feliciangeli et al, Cell. 2007, 130, 563-569). We now provide new evidence demonstrating that the lack of measurable current upon TWIK1 expression in mammalian cells is caused by its active endocytosis from cell surface and retention in intracellular recycling endosomes. Inactivation by point mutation of an unusual endocytosis signal sequence produces a mutated TWIK1 channel that is expressed at the cell surface and produces measurable currents in all the cell types that have been tested. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|