Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge.

Lesage, Florian; Reyes, Roberto V.; Fink, Michel; Duprat, Fabrice; Guillemare, Eric; Lazdunski, Michel

doi:10.1002/j.1460-2075.1996.tb01031.x

Cited by 160 publications

(129 citation statements)

References 45 publications

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“…Previous RT-PCR and in situ hybridization studies have revealed that TWIK-1 is present in the mammalian brain and also in a wide variety of tissues outside the nervous system (Lesage et al, 1996;Orias et al, 1997, Arrighi et al, 1998Wang et al,1998;Medhurst et al, 2001 andTalley et al, 2001). TWIK-1 expression has been previously shown in the cochlear nucleus using PCR (Holt et al, 2006) and in the inner ear and cochlear nucleus using in situ hybridization (Nicolas MT et al, 2003;Talley et al, 2001).…”

Section: Pcr Resultsmentioning

confidence: 99%

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

et al. 2007

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Two-pore potassium channels can influence neuronal excitability by regulating background leakage of potassium ions and resting membrane potential. The present study used quantitative real time PCR and in situ hybridization to determine if the decreased activity from deafness would induce changes in two-pore potassium channel subunit expression in the rat inferior colliculus. Ten subunits were assessed with qRT-PCR at 3 days, 3 weeks and 3 months following bilateral cochlear ablation. TASK-1, TASK-5 and THIK-2 showed significant decreases in expression at all three times assessed. TASK-5, relatively specific to auditory neurons, had the greatest decrease. TWIK-1 was significantly decreased at 3 weeks and 3 months following deafness and TREK-2 was only significantly decreased at 3 days. TASK-3, TWIK-2, THIK-1, TRAAK and TREK-1 did not show any significant changes in gene expression. In situ hybridization was used to examine TASK-1, TASK-5, TWIK-1 and THIK-2 in the central nucleus, dorsal cortex and lateral (external) cortex of the IC in normal hearing animals and at 3 weeks following deafening. All four subunits showed expression in neurons throughout IC subdivisions in normal hearing rats, with TASK-5 having the greatest overall number of labeled neurons. There was no co-localization of subunit expression with GFAP immunostaining, indicating no expression in glia. Three weeks following deafening there was a significant decrease in the number of neurons expressing TASK-1 and THIK-2 in the IC, while TASK-5 had significant decreases in the central nucleus and dorsal cortex and TWIK-1 in the lateral and dorsal cortices. Two-pore potassium channels (K 2p ) are a class of open rectifying potassium selective channels (Ketchum et al., 1995) that, when activated, allow a background leakage of potassium ions that raises the resting membrane potential to hyperpolarizing levels, resulting in decreased neuronal excitability (see Lesage and Lazdunski, 2000;Goldstein et al., 2001;Patel and Honore, 2001; Plant et al., 2005 for reviews). There are, to date, 18 subunits in the K 2p channel family that have been divided into different classes based on what is know about their sensitivities. The TASK-1 (K 2p 3.1, KCNK3), TASK-3 (K 2p 9.1, KCNK9) and TWIK-1 (K 2p 1.1, KCNK1) subunits are widely expressed throughout the brain but have been reported to have only moderate expression in the auditory brain stem Talley et al., 2001). The TASK-5 (K 2p 15.1, KCNK15) subunit has a relatively selective expression, primarily found in Author for correspondence: Dr. Richard A. Altschuler, KHRI, Department of Otolaryngology, The University of Michigan, 1301 East Ann Street, Ann Arbor, MI, Tel: (734) Fax: (734) 764-0014, E-mail: E-mail: shuler@umich.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof befo...

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Section: Pcr Resultsmentioning

confidence: 99%

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

et al. 2007

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“…The PLA probe antiRabbit MINUS binds to the TREK-1 antibody (Alomone Labs), whereas the PLA probe anti-Goat PLUS binds to the TWIK-1 antibody (Santa Cruz Biotechnology). If the distance between both proteins is o40 nm, a signal with DuoLink PLA is generated, thus indicating an interaction between both proteins 25 . After preincubation with a blocking agent for 1 h, the fixed astrocytes were incubated overnight with the primary antibodies to TREK-1 (Alomone Labs, 1:200) and TWIK-1 (Santa Cruz Biotechnology, 1:100).…”

Section: Methodsmentioning

confidence: 99%

“…Based on observations that TWIK-1 homodimerizes via a disulphide bridge 25,27 , a cysteine residue is located in the first extracellular loop of TREK-1 (Fig. 4a), and this cysteine residue is highly conserved in TWIK-1 and TREK-1 of several different species ( Supplementary Fig.…”

Section: Twik-1 Is a Functional Channel In Astrocytesmentioning

confidence: 99%

A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

et al. 2014

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TWIK-1 is a member of the two-pore domain K þ (K2P) channel family that plays an essential part in the regulation of resting membrane potential and cellular excitability. The physiological role of TWIK-1 has remained enigmatic because functional expression of TWIK-1 channels is elusive. Here we report that native TWIK-1 forms a functional channel at the plasma membrane of astrocytes. A search for TWIK-1-binding proteins led to the identification of TREK-1, another member of the K2P family. The TWIK-1/TREK-1 heterodimeric channel is formed via a disulphide bridge between residue C69 in TWIK-1 and C93 in TREK-1. Gene silencing demonstrates that surface expression of TWIK-1 and TREK-1 are interdependent. TWIK-1/TREK-1 heterodimers mediate astrocytic passive conductance and cannabinoidinduced glutamate release from astrocytes. Our study sheds new light on the diversity of K2P channels.

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“…sup-9(n2282) encodes an isoleucine instead of the initiator methionine and thus is likely to be a null allele. The mutations V41A, V44E, D58V, I61S, and A74V cause changes in the M1-P1 linker, which has been shown to act as a dimerization domain in vitro in the human TWIK-1 two-pore channel (Lesage et al, 1996).…”

Section: Characterization Of Sup-9 Mutant Allelesmentioning

confidence: 99%

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K⁺Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

et al. 2003

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Genetic studies of sup-9, unc-93, and sup-10 strongly suggest that these genes encode components of a multi-subunit protein complex that coordinates muscle contraction in Caenorhabditis elegans. We cloned sup-9 and sup-10 and found that they encode a two-pore K ϩ channel and a novel transmembrane protein, respectively. We also found that UNC-93 and SUP-10 colocalize with SUP-9 within muscle cells, and that UNC-93 is a member of a novel multigene family that is conserved among C. elegans, Drosophila, and humans. Our results indicate that SUP-9 and perhaps other two-pore K ϩ channels function as multiprotein complexes, and that UNC-93 and SUP-10 likely define new classes of ion channel regulatory proteins.

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Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge.

Cited by 160 publications

References 45 publications

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K⁺Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

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Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge.

Cited by 160 publications

References 45 publications

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K+Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

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sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K⁺Channel that Coordinates Muscle Contraction inCaenorhabditis elegans