TRESK background K(+) channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.

TRESK (TWIK-related spinal cord K(+) channel, KCNK18) is a major background K(+) channel of sensory neurons. Dominant-negative mutation of TRESK is linked to familial migraine. This important two-pore domain K(+) channel is uniquely activated by calcineurin. The calcium/calmodulin-dependent protein...

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Main Authors: Gabriella Braun, Balázs Nemcsics, Péter Enyedi, Gábor Czirják
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3228728?pdf=render
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spelling doaj-0d3078c110304442bec245443b05e3302020-11-25T02:10:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2811910.1371/journal.pone.0028119TRESK background K(+) channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.Gabriella BraunBalázs NemcsicsPéter EnyediGábor CzirjákTRESK (TWIK-related spinal cord K(+) channel, KCNK18) is a major background K(+) channel of sensory neurons. Dominant-negative mutation of TRESK is linked to familial migraine. This important two-pore domain K(+) channel is uniquely activated by calcineurin. The calcium/calmodulin-dependent protein phosphatase directly binds to the channel and activates TRESK current several-fold in Xenopus oocytes and HEK293 cells. We have recently shown that the kinase, which is responsible for the basal inhibition of the K(+) current, is sensitive to the adaptor protein 14-3-3. Therefore we have examined the effect of the 14-3-3-inhibited PAR-1/MARK, microtubule-associated-protein/microtubule affinity-regulating kinase on TRESK in the Xenopus oocyte expression system. MARK1, MARK2 and MARK3 accelerated the return of TRESK current to the resting state after the calcium-dependent activation. Several other serine-threonine kinase types, generally involved in the modulation of other ion channels, failed to influence TRESK current recovery. MARK2 phosphorylated the primary determinant of regulation, the cluster of three adjacent serine residues (S274, 276 and 279) in the intracellular loop of mouse TRESK. In contrast, serine 264, the 14-3-3-binding site of TRESK, was not phosphorylated by the kinase. Thus MARK2 selectively inhibits TRESK activity via the S274/276/279 cluster, but does not affect the direct recruitment of 14-3-3 to the channel. TRESK is the first example of an ion channel phosphorylated by the dynamically membrane-localized MARK kinases, also known as general determinants of cellular polarity. These results raise the possibility that microtubule dynamics is coupled to the regulation of excitability in the neurons, which express TRESK background potassium channel.http://europepmc.org/articles/PMC3228728?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Gabriella Braun
Balázs Nemcsics
Péter Enyedi
Gábor Czirják
spellingShingle Gabriella Braun
Balázs Nemcsics
Péter Enyedi
Gábor Czirják
TRESK background K(+) channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.
PLoS ONE
author_facet Gabriella Braun
Balázs Nemcsics
Péter Enyedi
Gábor Czirják
author_sort Gabriella Braun
title TRESK background K(+) channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.
title_short TRESK background K(+) channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.
title_full TRESK background K(+) channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.
title_fullStr TRESK background K(+) channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.
title_full_unstemmed TRESK background K(+) channel is inhibited by PAR-1/MARK microtubule affinity-regulating kinases in Xenopus oocytes.
title_sort tresk background k(+) channel is inhibited by par-1/mark microtubule affinity-regulating kinases in xenopus oocytes.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-01-01
description TRESK (TWIK-related spinal cord K(+) channel, KCNK18) is a major background K(+) channel of sensory neurons. Dominant-negative mutation of TRESK is linked to familial migraine. This important two-pore domain K(+) channel is uniquely activated by calcineurin. The calcium/calmodulin-dependent protein phosphatase directly binds to the channel and activates TRESK current several-fold in Xenopus oocytes and HEK293 cells. We have recently shown that the kinase, which is responsible for the basal inhibition of the K(+) current, is sensitive to the adaptor protein 14-3-3. Therefore we have examined the effect of the 14-3-3-inhibited PAR-1/MARK, microtubule-associated-protein/microtubule affinity-regulating kinase on TRESK in the Xenopus oocyte expression system. MARK1, MARK2 and MARK3 accelerated the return of TRESK current to the resting state after the calcium-dependent activation. Several other serine-threonine kinase types, generally involved in the modulation of other ion channels, failed to influence TRESK current recovery. MARK2 phosphorylated the primary determinant of regulation, the cluster of three adjacent serine residues (S274, 276 and 279) in the intracellular loop of mouse TRESK. In contrast, serine 264, the 14-3-3-binding site of TRESK, was not phosphorylated by the kinase. Thus MARK2 selectively inhibits TRESK activity via the S274/276/279 cluster, but does not affect the direct recruitment of 14-3-3 to the channel. TRESK is the first example of an ion channel phosphorylated by the dynamically membrane-localized MARK kinases, also known as general determinants of cellular polarity. These results raise the possibility that microtubule dynamics is coupled to the regulation of excitability in the neurons, which express TRESK background potassium channel.
url http://europepmc.org/articles/PMC3228728?pdf=render
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