Further Characterization of the Type 3 Ryanodine Receptor (RyR3) Purified from Rabbit Diaphragm

Murayama, Takashi; Ôba, Toshiharu; Katayama, Eisaku; Oyamada, Hideto; Oguchi, Katsuji; Kobayashi, Masakazu; Otsuka, Kazuyuki; Ogawa, Yasuo

doi:10.1074/jbc.274.24.17297

Cited by 89 publications

(119 citation statements)

References 52 publications

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“…When the other RyR subtypes were pharmacologically blocked in hippocampal slices from the RyR3 KO mice, the results were indistinguishable from those obtained from WT slices exposed to the same pharmacological conditions except for a significant (P Ͻ 0.001, paired t-test) change in baseline synaptic transmission following the addition of 10 M ryanodine (fEPSP slope ϭ 106 Ϯ 0.24% of baseline for WT and 95 Ϯ 0.51% of baseline for RyR3 KO). These changes in baseline synaptic transmission may be a result of this concentration of ryanodine (10 M) causing a long-lasting subconductance state rather than fully inhibiting activity of the receptor (Murayama et al 1999). Taken together, these data indicate that expression of superoxide-induced potentiation is mediated by RyR3 activation.…”

Section: Activation Of Ryr3 Is Necessary For Superoxideinduced Potentsupporting

confidence: 50%

“…RyR3 KO mice display significantly reduced LTP following various stimulation protocols (Balschun et al 1999;Shimuta et al 2001). Redox regulation of RyR3 receptors may partially mediate these effects as single-channel recordings indicate that oxidizing reagents activate the channel, whereas reducing reagents inhibit it (Murayama et al 1999). Thus it is possible that RyRs, most notably RyR3, modulate the magnitude of LTP via activation of ERK.…”

Section: Introductionmentioning

confidence: 99%

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Superoxide-Induced Potentiation in the Hippocampus Requires Activation of Ryanodine Receptor Type 3 and ERK

Huddleston

Tang

Takeshima

et al. 2008

Journal of Neurophysiology

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Huddleston AT, Tang W, Takeshima H, Hamilton SL, Klann E. Superoxide-induced potentiation in the hippocampus requires activation of tyanodine receptor type 3 and ERK. J Neurophysiol 99: 1565-1571, 2008. First published January 16, 2008 doi:10.1152/jn.00659.2007. Reactive oxygen species (ROS) are required for the induction of longterm potentiation (LTP) and behave as signaling molecules via redox modifications of target proteins. In particular, superoxide is necessary for induction of LTP, and application of superoxide to hippocampal slices is sufficient to induce LTP in area CA1. Although a rise in postsynaptic intracellular calcium is necessary for LTP induction, superoxide-induced potentiation does not require calcium flux through N-methyl-D-aspartate (NMDA) receptors. Ryanodine receptors (RyRs) mediate calcium-induced calcium release from intracellular stores and have been shown to modulate LTP. In this study, we investigated the highly redox-sensitive RyRs and L-type calcium channels as calcium sources that might mediate superoxide-induced potentiation. In agreement with previous studies of skeletal and cardiac muscle, we found that superoxide enhances activation of RyRs in the mouse hippocampus. We identified a functional coupling between L-type voltage-gated calcium channels and RyRs and identified RyR3, a subtype enriched in area CA1, as the specific isoform required for superoxide-induced potentiation. Superoxide also enhanced the phosphorylation of extracellular signal-regulated kinase (ERK) in area CA1, and ERK was necessary for superoxide-induced potentiation. Thus superoxide-induced potentiation requires the redox targeting of RyR3 and the subsequent activation of ERK.

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Section: Activation Of Ryr3 Is Necessary For Superoxideinduced Potentsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Superoxide-Induced Potentiation in the Hippocampus Requires Activation of Ryanodine Receptor Type 3 and ERK

Huddleston

Tang

Takeshima

et al. 2008

Journal of Neurophysiology

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“…The Ca 2+ dependence of WT RyR3 has been previously published based on immunoprecipitated protein and the resulting data fitted using a single-site model indicating monophasic activation of WT RyR3 by Ca 2+ [28] and [29]. Two significant methodological differences distinguish the present study.…”

Section: Resultsmentioning

confidence: 91%

“…1A. Indeed, at 5-10μM Ca 2+ , WT RyR3 was shown to exhibit increased subconductance behavior relative to WT RyR1 [28] and [33]. This correlation is additionally supported by increased subconductance behavior of brain WT RyRs at specific Ca 2+ and ATP concentrations [34].…”

Section: Mg 2+ Inhibitionmentioning

confidence: 79%

Allosterically coupled calcium and magnesium binding sites are unmasked by ryanodine receptor chimeras

Voss

Allen

Pessah

et al. 2008

Biochemical and Biophysical Research Communications

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We studied cation regulation of wild type ryanodine receptor type 1 ( WT RyR1), type 3 ( WT RyR3) and RyR3/RyR1 chimeras (Ch) expressed in 1B5 dyspedic myotubes. Using [ 3 H]ryanodine binding to sarcoplasmic reticulum (SR) membranes, Ca 2+ titrations with WT RyR3 and three chimeras show biphasic activation that is allosterically coupled to attenuated inhibition relative to WT RyR1. Chimeras show biphasic Mg 2+ inhibition profiles at 3 and 10μM Ca 2+ , no observable inhibition at 20μM Ca 2+ and monophasic inhibition at 100μM Ca 2+ . Ca 2+ imaging of intact myotubes expressing Ch-4 exhibit caffeine-induced Ca 2+ transients with inhibition kinetics that are significantly slower than those expressing WT RyR1 or WT RyR3. Four new aspects of RyR regulation are evident: 1) high affinity (H) activation and low affinity (L) inhibition sites are allosterically coupled, 2) Ca 2+ facilitates removal of the inherent Mg 2+ block, 3) WT RyR3 exhibits reduced cooperativity between H activation sites when compared to WT RyR1, and 4) uncoupling of these sites in Ch-4 results in decreased rates of inactivation of caffeine-induced Ca transients.Keywords ryanodine receptors; calcium-induced calcium release; channel regulation Three isoforms of wild type ryanodine receptors ( WT RyR1, 2 and 3) are expressed in specialized regions of endoplasmic/sarcoplasmic reticulum (ER/SR) in most mammalian cells where they function as Ca 2+ 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 before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Materials and Methods Chimeric RyR1/RyR3 constructsSpecific primers were designed for PCR amplification of the selected fragments using WT RyR1 as a template. Amplified fragments from WT RyR1 encoding aa 1681-2217 (Ch-17), 1924-2446 (Ch-21) and 1681-3770 (Ch-4) were inserted, in frame, into the endogenous restriction site(s) of HSV-RyR3 plasmid as described previously [20]. All chimeric constructs were cloned into the HSV-1 amplicon vector and packaged using a helper virus-free packaging system [22]. Cell culture, infection and membrane preparation1B5 myoblasts were cultured and differentiated into myotubes as described previously [20] and [23]. Plates with differentiated myotubes were infected with virion containing wild type and RyR1/RyR3 chimeric cDNA for 2 h and membrane extracts were prepared 36 h after infection. Myotubes were homogenized and membrane fractions obtained by differential centrifugation as described previously [24].[ cold buffer, placed into 5 ml scintillation cocktail (ScintiVerse; Fisher Scientific) and radioactivity counted. Equations for binding analysisCurve fitting was ...

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“…RyR1 and RyR3 are capable of binding both FKBP isoforms, whereas RyR2 binds only FKBP12.6. Purified RyR2 and RyR3 differ from RyR1 by their lack of modulation of channel activity by FKBP12 and FKBP12.6 (12,22,23). Despite the similarities of the isolated RyR isoforms, they are not functionally interchangeable in vivo, particularly with regard to their roles in e-c coupling (24 -28).…”

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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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Further Characterization of the Type 3 Ryanodine Receptor (RyR3) Purified from Rabbit Diaphragm

Cited by 89 publications

References 52 publications

Superoxide-Induced Potentiation in the Hippocampus Requires Activation of Ryanodine Receptor Type 3 and ERK

Superoxide-Induced Potentiation in the Hippocampus Requires Activation of Ryanodine Receptor Type 3 and ERK

Allosterically coupled calcium and magnesium binding sites are unmasked by ryanodine receptor chimeras

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

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