The Structure, Function, and Cellular Regulation of Ryanodine-Sensitive Ca2+ Release Channels

Shoshan‐Barmatz, Varda; Ashley, Richard H.

doi:10.1016/s0074-7696(08)60145-x

Cited by 81 publications

(69 citation statements)

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“…Eukaryotic cells contain functional channels in the endoplasmic reticulum and sarcoplasmic reticulum [1][2][3] ; specific ion channels have also been identified in the inner nuclear membrane [4], mitochondrial membranes [5,6], Golgi membranes [7,8] and secretory vesicles [9][10][11]. Some of these channels are involved in the mobilization of intracellular Ca# + [1,2] and the transport of metabolites [5].…”

Section: Introductionmentioning

confidence: 99%

“…Some of these channels are involved in the mobilization of intracellular Ca# + [1,2] and the transport of metabolites [5]. However, the molecular identities and cellular roles of many intracellular channels remain to be discovered.…”

Section: Introductionmentioning

confidence: 99%

“…1 Present address : Department of Chemistry, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima 30000, Thailand. 2 To whom correspondence should be addressed (e-mail richard.ashley!ed.ac.uk).…”

Section: Introductionmentioning

confidence: 99%

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Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms

Suginta

Karoulias

Aitken

et al. 2001

Biochemical Journal

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Mammalian chloride intracellular channel (CLIC) (p64-related) proteins are widely expressed, with an unusual dual localization as both soluble and integral membrane proteins. The molecular basis for their cellular localization and ion channel activity remains unclear. To help in addressing these problems, we identified novel rat brain CLIC4 (p64H1) binding partners by affinity chromatography, mass spectrometric analysis and microsequencing. Brain CLIC4 binds dynamin I, α-tubulin, β-actin, creatine kinase and two 14-3-3 isoforms ; the interactions are confirmed in i o by immunoprecipitation. Gel overlay and reverse pull-down assays indicate that the binding of CLIC4 to dynamin I and 14-3-3ζ is direct. In HEK-293 cells, biochemical and immunofluorescence analyses show partial co-localization of

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms

Suginta

Karoulias

Aitken

et al. 2001

Biochemical Journal

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“…1 Because of its high affinity and specificity, ryanodine has been widely used as a specific ligand for the identification, purification, cloning, and functional characterization of RyRs (1)(2)(3)(4)(5)(6)(7). The unique and specific action of ryanodine on RyR function also has made it an invaluable pharmacological probe for intracellular Ca 2ϩ signaling in a variety of cells (8,9), and for understanding the mechanisms of ion conduction and channel gating of RyRs (10,11).…”

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confidence: 99%

Ryanodine Sensitizes the Ca2+ Release Channel (Ryanodine Receptor) to Ca2+ Activation

Masumiya

Пин

Zhang

et al. 2001

Journal of Biological Chemistry

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Ryanodine, a plant alkaloid, is one of the most widely used pharmacological probes for intracellular Ca 2؉ signaling in a variety of muscle and non-muscle cells. Upon binding to the Ca 2؉ release channel (ryanodine receptor), ryanodine causes two major changes in the channel: a reduction in single-channel conductance and a marked increase in open probability. The molecular mechanisms underlying these alterations are not well understood. In the present study, we investigated the gating behavior and Ca 2؉ dependence of the wild type (wt) and a mutant cardiac ryanodine receptor (RyR2) after being modified by ryanodine. Single-channel studies revealed that the ryanodine-modified wt RyR2 channel was sensitive to inhibition by Mg 2؉ and to activation by caffeine and ATP. In the presence of Mg 2؉ , the ryanodine-modified single wt RyR2 channel displayed a sigmoidal Ca 2؉ dependence with an EC 50 value of 110 nM, whereas the ryanodine-unmodified single wt channel exhibited an EC 50 of 120 M for Ca 2؉ activation, indicating that ryanodine is able to increase the sensitivity of the wt RyR2 channel to Ca 2؉ activation by ϳ1,000-fold. Furthermore, ryanodine is able to restore Ca 2؉ activation and ligand response of the E3987A mutant RyR2 channel that has been shown to exhibit ϳ1,000-fold reduction in Ca 2؉ sensitivity to activation. The E3987A mutation, however, affects neither [ 3 H]ryanodine binding to nor the stimulatory and inhibitory effects of ryanodine on the RyR2 channel. These results demonstrate that ryanodine does not "lock" the RyR channel into an open state as generally believed; rather, it sensitizes dramatically the channel to activation by Ca 2؉ .Ryanodine, a plant alkaloid, binds specifically with high affinity to and alters the function of intracellular Ca 2ϩ release channels (ryanodine receptors, RyRs).

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“…Ryanodine receptors (RyRs) 1 and inositol 1,4,5-trisphosphate receptors are the two families of intracellular calcium release channels that have been characterized to date (reviewed in Refs. [2][3][4][5][6][7][8][9]. Both RyRs and inositol 1,4,5-trisphosphate receptors exist as homotetrameric protein complexes composed of an unusually large subunit, Ϸ560 kDa for RyRs and Ϸ313 kDa for inositol 1,4,5-trisphosphate receptors.…”

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confidence: 99%

Three-dimensional Structure of Ryanodine Receptor Isoform Three in Two Conformational States as Visualized by Cryo-electron Microscopy

Sharma¹,

Jeyakumar²,

Fleischer³

et al. 2000

Journal of Biological Chemistry

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Using cryo-electron microscopy and single particle image processing techniques, we present the first threedimensional reconstructions of isoform 3 of the ryanodine receptor/calcium release channel (RyR3). Reconstructions were carried out on images obtained from a purified, detergent-solubilized receptor for two different buffer conditions, which were expected to favor open and closed functional states of the channel. As for the heart (RyR2) and skeletal muscle (RyR1) receptor isoforms, RyR3 is a homotetrameric complex comprising two main components, a multidomain cytoplasmic assembly and a smaller (ϳ20% of the total mass) transmembrane region. Although the isoforms show structural similarities, consistent with the ϳ70% overall sequence identity of the isoforms, detailed comparisons of RyR3 with RyR1 showed one region of highly significant difference between them. This difference indicated additional mass present in RyR1, and it likely corresponds to a region of the RyR1 sequence (residues 1303-1406, known as diversity region 2) that is absent from RyR3. The reconstructions of RyR3 determined under "open" and "closed" conditions were similar to each other in overall architecture. A difference map computed between the two reconstructions reveals subtle changes in conformation at several widely dispersed locations in the receptor, the most prominent of which is a ϳ4°ro-tation of the transmembrane region with respect to the cytoplasmic assembly.

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The Structure, Function, and Cellular Regulation of Ryanodine-Sensitive Ca2+ Release Channels

Cited by 81 publications

References 397 publications

Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms

Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms

Ryanodine Sensitizes the Ca2+ Release Channel (Ryanodine Receptor) to Ca2+ Activation

Three-dimensional Structure of Ryanodine Receptor Isoform Three in Two Conformational States as Visualized by Cryo-electron Microscopy

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