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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Douguet, Dominique Lesage, Florian Chatelain, Franck C. Bichet, Delphine Braud, Véronique M. Feliciangeli, Sylvain Larroque, Marie-madeleine |
| Description | Author Affiliation: Chatelain FC ( From the Laboratory of Excellence Ion Channel Science and Therapeutics, Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, and Université de Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France.) |
| Abstract | The tandem pore domain halothane-inhibited K(+) channel 1 (THIK1) produces background K(+) currents. Despite 62% amino acid identity with THIK1, THIK2 is not active upon heterologous expression. Here, we show that this apparent lack of activity is due to a unique combination of retention in the endoplasmic reticulum and low intrinsic channel activity at the plasma membrane. A THIK2 mutant containing a proline residue (THIK2-A155P) in its second inner helix (M2) produces K(+)-selective currents with properties similar to THIK1, including inhibition by halothane and insensitivity to extracellular pH variations. Another mutation in the M2 helix (I158D) further increases channel activity and affects current kinetics. We also show that the cytoplasmic amino-terminal region of THIK2 (Nt-THIK2) contains an arginine-rich motif (RRSRRR) that acts as a retention/retrieval signal. Mutation of this motif in THIK2 induces a relocation of the channel to the plasma membrane, resulting in measurable currents, even in the absence of mutations in the M2 helix. Cell surface delivery of a Nt-THIK2-CD161 chimera is increased by mutating the arginines of the retention motif but also by converting the serine embedded in this motif to aspartate, suggesting a phosphorylation-dependent regulation of THIK2 trafficking. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 49 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-12-06 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Potassium Channels, Tandem Pore Domain Genetics Metabolism Amino Acid Sequence Amino Acid Substitution Animals Cell Membrane Endoplasmic Reticulum Gene Silencing Intracellular Space Madin Darby Canine Kidney Cells Membrane Potentials Molecular Sequence Data Mutagenesis, Site-Directed Oocytes Phosphorylation Chemistry Protein Structure, Secondary Recombinant Proteins Sequence Homology, Amino Acid Xenopus Laevis Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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