Three‐dimensional architecture of the skeletal muscle ryanodine receptor

Wagenknecht, Terence; Radermacher, Michael

doi:10.1016/0014-5793(95)00581-s

Cited by 39 publications

(17 citation statements)

References 33 publications

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“…Our anti-RyR3 antibody is directed against a peptidic sequence that is, according to the model of ten transmembrane segments [42,55,59], localized in the cytoplasmic loop between the transmembrane segments TM4 and TM5 of the RyR3. This region, highly conserved among species, is negatively charged and contains, in its carboxyl-terminal part, two glutamate residues that may play an important role in the sensitivity of RyR3 to calcium.…”

Section: Discussionmentioning

confidence: 99%

Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3-mediated calcium-induced calcium release

Vrede

Fossier

Baux

et al. 2007

Pflugers Arch - Eur J Physiol

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In several neuronal preparations, the ryanodine-sensitive calcium store was reported to participate in the generation of slow afterhyperpolarization currents (IsAHP) involved in spike frequency adaptation. We show that calcium release from the ryanodine-sensitive calcium store is a major determinant of the triggering of IsAHP in mouse CA1 pyramidal neurons. Whole-cell patch clamp recordings in hippocampus slices show that the intracellular calcium stores depletion using an inhibitor of the endoplasmic reticulum Ca2+-ATPase (5 microM cyclopiazonic acid), as well as the specific blockade of ryanodine receptors (100 microM ryanodine) both reduced the IsAHP by about 70%. Immunohistology, using an anti-RyR3 specific antibody, indicates that RyR3 expression is particularly enriched in the CA1 apical dendrites (considered as the most important site for sAHP generation). We show that our anti-RyR3 antibody acts as a functional RyR3 antagonist and induced a reduction in IsAHP by about 70%. The additional ryanodine application (100 micro M) did not further affect IsAHP, thus excluding RyR2 in IsAHP activation. Our results argue in favor of a specialized function of RyR3 in CA1 pyramidal cells in triggering IsAHP due to their localization in the apical dendrite.

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Section: Discussionmentioning

confidence: 99%

Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3-mediated calcium-induced calcium release

Vrede

Fossier

Baux

et al. 2007

Pflugers Arch - Eur J Physiol

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“…If these sequences formed a hairpin loop, a long sequence would lie in the lumen. No such mass has been observed in the structure of RyR1 (18,19). In the C-terminal end of RyR1, stretches of amino acids for which the average index for each amino acid is Ͼ1 include Glu-4275-Ala-4300 (average index 1.137), Thr-4323-Gly-4363 (1.197), Arg-4557-Ile-4576 (1.241), Gly-4637-Asn-4662 (1.170), Gln-4776-Thr-4825 (1.092), Gly-4834-Val-4854 (1.201), and Leu-4911-Leu-4935 (1.253).…”

Section: Prediction Of Transmembrane Helices and Strategy For Designingmentioning

confidence: 95%

“…From these studies, it has been possible to estimate the mass of protein contained in the transmembrane domains, based on the total volume of the transmembrane domain and the volume occupied by a transmembrane helix (18,19). The intramembrane domain could accommodate 24-32 transmembrane helices (18), suggesting that the most likely number of transmembrane helices per monomer is between 6 and 8.…”

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confidence: 99%

Topology of the Ca ²⁺ release channel of skeletal muscle sarcoplasmic reticulum (RyR1)

Sandhu

Khanna

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

132

110

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To define the topology of the skeletal muscle ryanodine receptor (RyR1), enhanced GFP (EGFP) was fused in-frame to the C terminus of RyR1, replacing a series of C-terminal deletions that started near the beginning or the end of predicted transmembrane helices M1-M10. The constructs were expressed in HEK-293 (human embryonic kidney cell line 293) or mouse embryonic fibroblast (MEF) cells, and confocal microscopy of intact and saponin-permeabilized cells was used to determine the subcellular location of the truncated fusion proteins. The fusion protein truncated after M3 exhibited uniform cytoplasmic fluorescence, which was lost after permeabilization, indicating that proposed M , M , M1, M2, and M3 sequences are not membrane-associated. The fusion protein truncated at the end of the M4 -M5 loop and containing M4 was membrane-associated. All longer truncated fusion proteins were also associated with intracellular membranes. Mapping by protease digestion and extraction of isolated microsomes demonstrated that EGFP positioned after either M5, the N-terminal half of M7 (M7a), or M8 was located in the lumen, and that EGFP positioned after either M4, M6, the C-terminal half of M7 (M7b), or M10 was located in the cytoplasm. These results indicate that RyR1 contains eight transmembrane helices, organized as four hairpin loops. The first hairpin is likely to be made up of M4a-M4b. However, it could be made up from M3-M4, which might form a hairpin loop even though M3 alone is not membrane-associated. The other three hairpin loops are formed from M5-M6, M7a-M7b, and M8 -M10. M9 is not a transmembrane helix, but it might form a selectivity filter between M8 and M10.S keletal muscle contraction is initiated by activation of a Ca 2ϩ release channel (ryanodine receptor isoform 1 or RyR1) located in the junctional terminal cisternae of the sarcoplasmic reticulum. Activation occurs through physical interaction with the dihydropyridine receptor, located in the transverse tubular membrane, where it is directly apposed to the ryanodine receptor (1, 2). Four RyR monomers, each of 565 kDa, assemble as a homotetrameric complex and transmembrane sequences from each of the four monomers interact to form the ion-conducting pore (3). Hydropathy profiles of RyR1 (4, 5), based on criteria defined by Kyte and Doolittle (6), indicate that the bulk of the RyR1 molecule is cytoplasmic and that 4-12 transmembrane sequences lie within the C-terminal one-tenth to one-fifth of the molecule. Among the predicted transmembrane sequences, four potential transmembrane sequences are clearly more hydrophobic than others, with hydropathy indices between 2.0 and 2.9. These four sequences, amino acids Phe-4564-Tyr-4580, Pro-4641-Leu-4664, Gln-4836 -Phe-4859, and Ile-4918 -Ile-4937, were designated M1-M4 and were proposed to form two hairpin loops in the topological model proposed by Takeshima et al. (4). In a second model, proposed by Zorzato et al. Earlier attempts have been made to elucidate the structure and topology of RyR. Proteolytic digestion of RyR1 ...

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“…In this model the dihydropyridine receptors are arranged in groups of four (tetrads), which appear to be in register with the tetrameric RyR1 s in the opposing junctional SR (6,(45)(46)(47). Accordingly, it appears that each dihydropyridine receptor within a tetrad would interact with one of the clamp assemblies in the adjoining RyR1 (39,48,49). Thus, the location that we have assigned to the D2 region in the three-dimensional structure of RyR appears to be consistent with current models of the triad junction's architecture.…”

Section: Fig 6 Comparison Of Ryr3 and Ryr1 Reconstructionsmentioning

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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Three‐dimensional architecture of the skeletal muscle ryanodine receptor

Cited by 39 publications

References 33 publications

Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3-mediated calcium-induced calcium release

Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3-mediated calcium-induced calcium release

Topology of the Ca ²⁺ release channel of skeletal muscle sarcoplasmic reticulum (RyR1)

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

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Three‐dimensional architecture of the skeletal muscle ryanodine receptor

Cited by 39 publications

References 33 publications

Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3-mediated calcium-induced calcium release

Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3-mediated calcium-induced calcium release

Topology of the Ca 2+ release channel of skeletal muscle sarcoplasmic reticulum (RyR1)

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

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Topology of the Ca ²⁺ release channel of skeletal muscle sarcoplasmic reticulum (RyR1)