Antagonistic Effect of a Cytoplasmic Domain on the Basal Activity of Polymodal Potassium Channels

Autor: Sylvain Feliciangeli, Ismail Ben Soussia, Franck C. Chatelain, Frank S. Choveau, Eun-Jin Kim, Delphine Bichet, Sandy Blin, Florian Lesage, Dawon Kang
Přispěvatelé: Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Department of Applied Mathematics [Sheffield], University of Sheffield [Sheffield], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Gyeongsang National University
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
resting membrane potential
structure function analysis
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV]Life Sciences [q-bio]
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
lcsh:RC321-571
03 medical and health sciences
Cellular and Molecular Neuroscience
Basal (phylogenetics)
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
excitability
parasitic diseases
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Molecular Biology
Inhibitory effect
PIP2 – phosphatidylinositol-4
ComputingMilieux_MISCELLANEOUS
Membrane potential
Chemistry
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
Differential regulation
bacterial infections and mycoses
Potassium channel
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
030104 developmental biology
Cytoplasm
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Biophysics
[SDV.IMM]Life Sciences [q-bio]/Immunology
5-bisphosphate
hormones
hormone substitutes
and hormone antagonists
potassium channel
Zdroj: Frontiers in Molecular Neuroscience
Frontiers in Molecular Neuroscience, Frontiers Media, 2018, 11, ⟨10.3389/fnmol.2018.00301⟩
Frontiers in Molecular Neuroscience, Vol 11 (2018)
ISSN: 1662-5099
DOI: 10.3389/fnmol.2018.00301⟩
Popis: TREK/TRAAK channels are polymodal K+ channels that convert very diverse stimuli, including bioactive lipids, mechanical stretch and temperature, into electrical signals. The nature of the structural changes that regulate their activity remains an open question. Here, we show that a cytoplasmic domain (the proximal C-ter domain, pCt) exerts antagonistic effects in TREK1 and TRAAK. In basal conditions, pCt favors activity in TREK1 whereas it impairs TRAAK activity. Using the conformation-dependent binding of fluoxetine, we show that TREK1 and TRAAK conformations at rest are different, and under the influence of pCt. Finally, we show that depleting PIP2 in live cells has a more pronounced inhibitory effect on TREK1 than on TRAAK. This differential regulation of TREK1 and TRAAK is related to a previously unrecognized PIP2-binding site (R329, R330, and R331) present within TREK1 pCt, but not in TRAAK pCt. Collectively, these new data point out pCt as a major regulatory domain of these channels and suggest that the binding of PIP2 to the pCt of TREK1 results in the stabilization of the conductive conformation in basal conditions.
Databáze: OpenAIRE
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