H3 Domain of Syntaxin 1A Inhibits KATP Channels by Its Actions on the Sulfonylurea Receptor 1 Nucleotide-Binding Folds-1 and -2

Cui, Ningren; Kang, Youhou; He, Yan; Leung, Yuk‐Man; Xie, Huanli; Pasyk, Ewa A.; Gao, Xiao‐Dong; Sheu, Laura; Hansen, John Bondo; Wahl, Philip; Tsushima, Robert G.; Gaisano, Herbert Y.

doi:10.1074/jbc.m410171200

Cited by 35 publications

(39 citation statements)

References 28 publications

(38 reference statements)

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“…Dialyzing 1 M Syn-1A into the cell reduced the currents by 33% (Fig. 3, A and C), similar to our previous report (23 ] ϭ 1.00 mM and [MgATP] ϭ 0.90 mM) in the pipette, maximum current density developed was 53 Ϯ 13 pA/pF. However, dialyzing 1 M Syn-1A into the cells did not significantly reduce the currents (Fig.…”

Section: Atp Dose-dependently Inhibits Syn-1a Binding To Sur1-supporting

confidence: 72%

“…Our previous studies have shown that Syn-1A binds to NBF1 and NBF2 domains of SUR subunits to regu- late K ATP channel activity in both rat pancreatic ␤-cells (22,23) and cardiac ventricular myocytes (21,33 (34) and K ATP channel (9). ATP and ADP regulate K ATP channel activity by interaction with two physically distinct sites on the channel.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies (22,23) showed that Syn-1A binds SUR1 at its NBF1 and NBF2 domains and would not bind Kir6.2. In addition, the physical interaction between SNAP-25 and SUR1 was not observed.…”

Section: Atp Dose-dependently Inhibits Syn-1a Binding To Sur1-mentioning

confidence: 99%

“…Electrophysiology-Rat islet ␤-cells isolated from male Sprague-Dawley as described previously were voltage-clamped in a whole-cell configuration (23). The typical pipette resistance was 3-5 M⍀.…”

Section: Constructs and Recombinant Gst-fusion Proteins-pgex-mentioning

confidence: 99%

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ATP Modulates Interaction of Syntaxin-1A with Sulfonylurea Receptor 1 to Regulate Pancreatic β-Cell KATP Channels

Kang

Zhang

Liang

et al. 2011

Journal of Biological Chemistry

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ATP-sensitive potassium (K ATP ) channels are regulated by a variety of cytosolic factors (adenine nucleotides, Mg2؉ , phospholipids, and pH). We previously reported that K ATP channels are also regulated by endogenous membrane-bound SNARE protein syntaxin-1A (Syn-1A), which binds both nucleotide-binding folds of sulfonylurea receptor (SUR)1 and 2A, causing inhibition of K ATP channel activity in pancreatic islet ␤-cells and cardiac myocytes, respectively. In this study, we show that ATP dose-dependently inhibits Syn-1A binding to SUR1 at physiological concentrations, with the addition of Mg 2؉ causing a decrease in the ATP-induced inhibitory effect. This ATP disruption of Syn-1A binding to SUR1 was confirmed by FRET analysis in living HEK293 cells. Electrophysiological studies in pancreatic ␤-cells demonstrated that reduced ATP concentrations increased K ATP channel sensitivity to Syn-1A inhibition. Depletion of endogenous Syn-1A in insulinoma cells by botulinum neurotoxin C1 proteolysis followed by rescue with exogenous Syn-1A showed that Syn-1A modulates K ATP channel sensitivity to ATP. Thus, our data indicate that although both ATP and Syn-1A independently inhibit ␤-cell K ATP channel gating, they could also influence the sensitivity of K ATP channels to each other. These findings provide new insight into an alternate mechanism by which ATP regulates pancreatic ␤-cell K ATP channel activity, not only by its direct actions on Kir6.2 pore subunit, but also via ATP modulation of Syn-1A binding to SUR1.The ATP-sensitive potassium (K ATP ) 3 channel couples intracellular metabolic changes to plasma membrane electrical activity in many cell types (1-3). In pancreatic ␤-cells, increase in ATP/ADP ratio from glucose metabolism closes plasma membrane K ATP channels, causing membrane depolarization that leads to opening of L-type voltage-dependent calcium channels. Ensuing calcium influx triggers exocytosis of docked and primed insulin granules in part by acting on the exocytic SNARE (soluble NSF attachment protein receptor) complex (4). The pancreatic ␤-cell K ATP channel is a heterooctamer of pore-forming Kir 6.2 and regulatory sulfonylurea receptor 1 (SUR1) subunits, with a 4:4 stoichiometry (5-7). SURs are members of the ATP-binding cassette protein superfamily (8), including cystic fibrosis transmembrane conductance regulator and P-glycoprotein/MDR1 (multidrug resistance 1). These ATP-binding cassette proteins uniformly contain two nucleotide-binding folds (NBF1 and NBF2), with each NBF containing Walker A and B motifs, which are sites of the action by adenine nucleotides. Regulation of K ATP channels by adenine nucleotides is complex, with ATP and ADP having both stimulatory and inhibitory effects (9 -11). Structure-function studies have demonstrated that ATP inhibits channel activity by interactions with Kir6.2 (12), whereas ADP acts on the SUR subunit to stimulate channel activity in an Mg 2ϩ -dependent manner (13). The importance of SUR1 as a regulator of K ATP channel activity is demonstrated by the fact th...

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Section: Atp Dose-dependently Inhibits Syn-1a Binding To Sur1-supporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Atp Dose-dependently Inhibits Syn-1a Binding To Sur1-mentioning

confidence: 99%

Section: Constructs and Recombinant Gst-fusion Proteins-pgex-mentioning

confidence: 99%

See 2 more Smart Citations

ATP Modulates Interaction of Syntaxin-1A with Sulfonylurea Receptor 1 to Regulate Pancreatic β-Cell KATP Channels

Kang

Zhang

Liang

et al. 2011

Journal of Biological Chemistry

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“…K ATP channel activity is suppressed by a SNARE protein, syntaxin 1A, via protein-protein interactions with the SUR subunits [72][73][74][75] . Syntaxin 1A decreases the activity [76] and the membrane expression level of K ATP channels [77] . Syntaxin 1A binding to the SUR1 subunit also attenuates the effect of K + channel openers, such as diazoxide, NNC55-0462, P1075, and cromakalim [78,79] .…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia

Sun

Feng

2012

Acta Pharmacol Sin

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ATP-sensitive potassium (K ATP ) channels are weak, inward rectifiers that couple metabolic status to cell membrane electrical activity, thus modulating many cellular functions. An increase in the ADP/ATP ratio opens K ATP channels, leading to membrane hyperpolarization. K ATP channels are ubiquitously expressed in neurons located in different regions of the brain, including the hippocampus and cortex. Brief hypoxia triggers membrane hyperpolarization in these central neurons. In vivo animal studies confirmed that knocking out the Kir6.2 subunit of the K ATP channels increases ischemic infarction, and overexpression of the Kir6.2 subunit reduces neuronal injury from ischemic insults. These findings provide the basis for a practical strategy whereby activation of endogenous K ATP channels reduces cellular damage resulting from cerebral ischemic stroke. K ATP channel modulators may prove to be clinically useful as part of a combination therapy for stroke management in the future.

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ATP-Sensitive Potassium Channels (KATP) Play a Role in Hypoxic Preconditioning Against Neonatal Hypoxic-Ischemic Brain Injury

Feng

Sun

2017

Springer Series in Translational Stroke Research

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H3 Domain of Syntaxin 1A Inhibits KATP Channels by Its Actions on the Sulfonylurea Receptor 1 Nucleotide-Binding Folds-1 and -2

Cited by 35 publications

References 28 publications

ATP Modulates Interaction of Syntaxin-1A with Sulfonylurea Receptor 1 to Regulate Pancreatic β-Cell KATP Channels

ATP Modulates Interaction of Syntaxin-1A with Sulfonylurea Receptor 1 to Regulate Pancreatic β-Cell KATP Channels

Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia

ATP-Sensitive Potassium Channels (KATP) Play a Role in Hypoxic Preconditioning Against Neonatal Hypoxic-Ischemic Brain Injury

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