PMID- 24163367
OWN - NLM
STAT- MEDLINE
DCOM- 20140213
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 49
DP  - 2013 Dec 6
TI  - Silencing of the tandem pore domain halothane-inhibited K+ channel 2 (THIK2) 
      relies on combined intracellular retention and low intrinsic activity at the 
      plasma membrane.
PG  - 35081-92
LID - 10.1074/jbc.M113.503318 [doi]
AB  - 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.
FAU - Chatelain, Franck C
AU  - Chatelain FC
AD  - From the Laboratory of Excellence Ion Channel Science and Therapeutics, Institut 
      de Pharmacologie Moleculaire et Cellulaire, CNRS, and Universite de Nice Sophia 
      Antipolis, 660 Route des Lucioles, 06560 Valbonne, France.
FAU - Bichet, Delphine
AU  - Bichet D
FAU - Feliciangeli, Sylvain
AU  - Feliciangeli S
FAU - Larroque, Marie-Madeleine
AU  - Larroque MM
FAU - Braud, Veronique M
AU  - Braud VM
FAU - Douguet, Dominique
AU  - Douguet D
FAU - Lesage, Florian
AU  - Lesage F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131025
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (KCNK12 protein, human)
RN  - 0 (KCNK13 protein, human)
RN  - 0 (Potassium Channels, Tandem Pore Domain)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Cell Membrane/metabolism
MH  - Dogs
MH  - Endoplasmic Reticulum/metabolism
MH  - Female
MH  - Gene Silencing
MH  - Humans
MH  - Intracellular Space/metabolism
MH  - Madin Darby Canine Kidney Cells
MH  - Membrane Potentials
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Oocytes/metabolism
MH  - Phosphorylation
MH  - Potassium Channels, Tandem Pore Domain/chemistry/*genetics/*metabolism
MH  - Protein Structure, Secondary
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Xenopus laevis
PMC - PMC3853260
OTO - NOTNLM
OT  - Electrophysiology
OT  - Endoplasmic Reticulum (ER)
OT  - Gating
OT  - Plasma Membrane
OT  - Potassium Channels
OT  - Protein Phosphorylation
OT  - Trafficking
EDAT- 2013/10/29 06:00
MHDA- 2014/02/14 06:00
PMCR- 2014/12/06
CRDT- 2013/10/29 06:00
PHST- 2013/10/29 06:00 [entrez]
PHST- 2013/10/29 06:00 [pubmed]
PHST- 2014/02/14 06:00 [medline]
PHST- 2014/12/06 00:00 [pmc-release]
AID - S0021-9258(20)55377-5 [pii]
AID - M113.503318 [pii]
AID - 10.1074/jbc.M113.503318 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Dec 6;288(49):35081-92. doi: 10.1074/jbc.M113.503318. Epub 2013 
      Oct 25.