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AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K(+) channels into open leak channels
- Source :
- EMBO Journal, EMBO Journal, EMBO Press, 2006, 25 (24), pp.5864-72. ⟨10.1038/sj.emboj.7601437⟩, EMBO Journal, 2006, 25 (24), pp.5864-72. ⟨10.1038/sj.emboj.7601437⟩
- Publication Year :
- 2006
- Publisher :
- HAL CCSD, 2006.
-
Abstract
- TREK channels are unique among two-pore-domain K(+) channels. They are activated by polyunsaturated fatty acids (PUFAs) including arachidonic acid (AA), phospholipids, mechanical stretch and intracellular acidification. They are inhibited by neurotransmitters and hormones. TREK-1 knockout mice have impaired PUFA-mediated neuroprotection to ischemia, reduced sensitivity to volatile anesthetics and altered perception of pain. Here, we show that the A-kinase-anchoring protein AKAP150 is a constituent of native TREK-1 channels. Its binding to a key regulatory domain of TREK-1 transforms low-activity outwardly rectifying currents into robust leak conductances insensitive to AA, stretch and acidification. Inhibition of the TREK-1/AKAP150 complex by Gs-coupled receptors such as serotonin 5HT4sR and noradrenaline beta2AR is as extensive as for TREK-1 alone, but is faster. Inhibition of TREK-1/AKAP150 by Gq-coupled receptors such as serotonin 5HT2bR and glutamate mGluR5 is much reduced when compared to TREK-1 alone. The association of AKAP150 with TREK channels integrates them into a postsynaptic scaffold where both G-protein-coupled membrane receptors (as demonstrated here for beta2AR) and TREK-1 dock simultaneously.
- Subjects :
- Proteomics
MESH: Hydrogen-Ion Concentration
Xenopus
MESH: Amino Acid Sequence
MESH: Dogs
chemistry.chemical_compound
Mice
MESH: Protein Structure, Tertiary
0302 clinical medicine
Postsynaptic potential
Chlorocebus aethiops
MESH: Up-Regulation
MESH: Animals
MESH: Xenopus
Receptor
MESH: Receptors, Cell Surface
0303 health sciences
Arachidonic Acid
General Neuroscience
MESH: Proteomics
Glutamate receptor
MESH: Potassium Channels, Tandem Pore Domain
Hydrogen-Ion Concentration
Up-Regulation
MESH: COS Cells
MESH: GTP-Binding Protein alpha Subunits, Gq-G11
Biochemistry
COS Cells
Arachidonic acid
Protein Binding
endocrine system
Molecular Sequence Data
Receptors, Cell Surface
Biology
General Biochemistry, Genetics and Molecular Biology
Article
MESH: Oocytes
03 medical and health sciences
Dogs
Potassium Channels, Tandem Pore Domain
Cell surface receptor
MESH: Mice, Inbred C57BL
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Animals
MESH: Protein Binding
Amino Acid Sequence
Molecular Biology
MESH: Mice
Ion channel
030304 developmental biology
G protein-coupled receptor
Adaptor Proteins, Signal Transducing
MESH: Adaptor Proteins, Signal Transducing
MESH: Molecular Sequence Data
General Immunology and Microbiology
MESH: Cercopithecus aethiops
Protein Structure, Tertiary
MESH: Arachidonic Acid
Mice, Inbred C57BL
chemistry
Biophysics
Oocytes
GTP-Binding Protein alpha Subunits, Gq-G11
Serotonin
Receptors, Adrenergic, beta-2
human activities
MESH: Receptors, Adrenergic, beta-2
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 02614189 and 14602075
- Database :
- OpenAIRE
- Journal :
- EMBO Journal, EMBO Journal, EMBO Press, 2006, 25 (24), pp.5864-72. ⟨10.1038/sj.emboj.7601437⟩, EMBO Journal, 2006, 25 (24), pp.5864-72. ⟨10.1038/sj.emboj.7601437⟩
- Accession number :
- edsair.doi.dedup.....e9bc8ee4bb589ecdcdbd31285d967ea2