Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A key event in skeletal muscle activation is the rapid release of Ca(2+) from the sarcoplasmic reticulum (SR), the Ca(2+) storage organelle in the muscle cell. The surface membrane/transverse tubules and the SR form functional units (calcium release units containing one or two couplons or junctions), where the voltage-sensing dihydropyridine receptor of the surface membrane interacts with the SR Ca(2+) release channel [ryanodine receptor (RyR)] and depolarization of the cell membrane is converted into Ca(2+) release from the SR. Although RyR1 is the most important isoform in skeletal muscle, some muscles also express high levels of RyR3, an isoform with a wide tissue distribution. The cytoplasmic domains of RyRs are visible in the electron microscope as periodically disposed feet. We find that, in muscles containing only RyR1, feet are exclusively located over the junctional SR surface facing the surface membrane/transverse tubule. In muscles containing RyR1 as well as RyR3, additional feet are located in lateral parajunctional regions immediately adjacent to junctional SR. Biochemical content of RyR3 and content of parajunctional feet are highly correlated in different muscles and the disposition of parajunctional versus junctional feet are notably different. On the basis of these two observations, we postulate that RyR3s are restricted to the parajunctional region, and thus their activation must be indirect and derivative during excitation-contraction coupling.
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PMID:Type 3 ryanodine receptors of skeletal muscle are segregated in a parajunctional position. 1181 57

The properties of ryanodine receptors (RyRs) from rat dorsal root ganglia (DRGs) have been studied. The density of RyRs (Bmax) determined by [3H]ryanodine binding was 63 fmol/mg protein with a dissociation constant (Kd) of 1.5 nM. [3H]Ryanodine binding increased with caffeine, decreased with ruthenium red and tetracaine, and was insensitive to millimolar concentrations of Mg2+ or Ca2+. DRG RyRs reconstituted in planar lipid bilayers were Ca2+-dependent and displayed the classical long-lived subconductance state in response to ryanodine; however, unlike cardiac and skeletal RyRs, they lacked Ca2+-dependent inactivation. Antibodies against RyR3, but not against RyR1 or RyR2, detected DRG RyRs. Thus, DRG RyRs are immunologically related to RyR3, but their lack of divalent cation inhibition is unique among RyR subtypes.
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PMID:Functional properties of ryanodine receptors from rat dorsal root ganglia. 1182 Oct 55

Most adult mammalian skeletal muscles contain only one isoform of ryanodine receptor (RyR1), whereas neonatal muscles contain two isoforms (RyR1 and RyR3). Membrane depolarization fails to evoke calcium release in muscle cells lacking RyR1, demonstrating an essential role for this isoform in excitation-contraction coupling. In contrast, the role of RyR3 is unknown. We studied the participation of RyR3 in calcium release in wild type (containing both RyR1 and RyR3 isoforms) and RyR3-/- (containing only RyR1) myotubes in the presence or absence of imperatoxin A (IpTxa), a high-affinity agonist of ryanodine receptors. IpTxa significantly increased the amplitude and the rate of release only in wild-type myotubes. Calcium currents, recorded simultaneously with the transients, were not altered with IpTxa treatment. [(3)H]ryanodine binding to RyR1 or RyR3 was significantly increased in the presence of IpTxa. Additionally, IpTxa modified the gating and conductance level of single RyR1 or RyR3 channels when studied in lipid bilayers. Our data show that IpTxa can interact with both RyRs and that RyR3 is functional in myotubes and it can amplify the calcium release signal initiated by RyR1, perhaps through a calcium-induced mechanism. In addition, our data indicate that when RyR3-/- myotubes are voltage-clamped, the effect of IpTxa is not detected because RyR1s are under the control of the dihydropyridine receptor.
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PMID:Imperatoxin a enhances Ca(2+) release in developing skeletal muscle containing ryanodine receptor type 3. 1186 48

Ryanodine receptors (RyRs) are expressed on the endoplasmic reticulum of many cells, where they form intracellular Ca2+-release channels that participate in the generation of intracellular Ca2+ signals. Here we report studies on the intracellular localisation and functional properties of transfected RyR1 or RyR3 channels in HEK 293 cells. Immunofluorescence studies indicated that both RyR1 and RyR3 did not form clusters but were homogeneously distributed throughout the endoplasmic reticulum. Ca2+ release experiments showed that transfected RyR1 and RyR3 channels responded to caffeine, although with different sensitivity, generating a global release of Ca2+ from the entire endoplasmic reticulum. However, video imaging and confocal microscopy analysis revealed that, in RyR3-expressing cells, local spontaneous Ca2+ release events were observed. No such spontaneous activity was observed in RyR1-expressing cells or in control cells. Interestingly, the spontaneous release events observed in RyR3-expressing cells were restricted to one or two regions of the endoplasmic reticulum, suggesting the formation of a further subcellular organisation of RyR3 in Ca2+ release units. These results demonstrate that different RyR isoforms can engage in the generation of distinct intracellular Ca2+ signals in HEK 293 cells.
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PMID:RyR1 and RyR3 isoforms provide distinct intracellular Ca2+ signals in HEK 293 cells. 1204 20

Three ryanodine receptor (RyR) isoforms, RyR1, RyR2, and RyR3, are expressed in mammalian tissues. It is unclear whether RyR isoforms are capable of forming heteromeric channels. To investigate their ability to form heteromeric channels, we co-expressed different RyR isoforms in HEK293 cells and examined their interactions biochemically and functionally. Immunoprecipitation studies revealed that RyR2 is able to interact physically with RyR3 and RyR1 in HEK293 cells and that RyR1 does not interact with RyR3. Co-expression of a ryanodine binding deficient mutant of RyR2, RyR2 (I4827T), with RyR3 (wt) restored [(3)H]ryanodine binding to the mutant. Interactions between RyR isoforms were further assessed by complementation analysis using mutants RyR2 (I4827T), RyR2 (E3987A), RyR3 (I4732T), RyR3 (E3885A), and RyR1 (E4032A), all of which are deficient in caffeine response. Caffeine-induced Ca(2+) release was restored in HEK293 cells co-transfected with mutants RyR2 (I4827T) and RyR3 (E3885A), RyR2 (E3987A) and RyR3 (I4732T), or RyR2 (I4827T) and RyR1 (E4032A), but not with RyR1 (E4032A) and RyR3 (I4732T), indicating that mutants of RyR2 and RyR3, or RyR2 and RyR1, but not RyR1 and RyR3, are able to complement each other. Co-expression of RyR3 (wt) and a pore mutant of RyR2, RyR2 (G4824A), produced regulatable single channels with intermediate unitary conductances. These observations demonstrate that RyR2 is capable of forming functional heteromeric channels with RyR3 and RyR1, whereas RyR1 is incapable of forming heteromeric channels with RyR3.
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PMID:Isoform-dependent formation of heteromeric Ca2+ release channels (ryanodine receptors). 1221 30

Ryanodine receptors (RyRs) are large, high conductance Ca2+ channels that control the level of intracellular Ca2+ by releasing Ca2+ from an intracellular compartment, the sarco/endoplasmic reticulum. Mammalian tissues express 3 closely related ryanodine receptors (RyRs) known as skeletal muscle (RyR1), cardiac muscle (RyR2) and brain (RyR3). The RyRs are isolated as 30S protein complexes comprised of four 560 kDa RyR2 subunits and four 12.6 kDa FK506 binding protein (FKBP12.6) subunits. Multiple endogenous effector molecules and posttranslational modifications regulate the RyRs. This chapter reviews the regulation of the mammalian RyRs by endogenous effector molecules.
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PMID:Regulation of mammalian ryanodine receptors. 1243 18

The family of ryanodine receptor (RyR) genes encodes three highly related Ca2+ release channels: RyR1, RyR2 and RyR3. Until about 10 years ago, RyRs were essentially known only for being the Ca2+ release channels of the sarcoplasmic reticulum of striated muscles, because of the high levels of expression of the RyR1 and RyR2 isoforms in skeletal and cardiac muscles, respectively. In contrast with the above picture, the RyR3 gene has been found not to be preferentially expressed in one specific tissue, but rather to be widely expressed in various cells. This wide expression pattern has been subsequently observed also for the RyR1 and RyR2 genes, which in addition to their preferential expression in striated muscles, have been found expressed also in several other cell types, although at lower levels than in striated muscles. Thus a closer look reveals that in several cells of vertebrates two or even three RyR isoforms can be co-expressed. In this chapter we will review published work on the RyR3 gene and discuss a model where co-expression of different RyR channel isoforms is interpreted as an evolutionary solution to provide, by functional interactions of distinct isoforms of Ca2+ release channels, the several types of vertebrate cells with the cell-specific Ca2+ release machinery required for generating the sophisticated intracellular Ca2+ signals needed for optimal regulation of their functions.
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PMID:Ryanodine receptor type 3: why another ryanodine receptor isoform? 1245 8

Ryanodine receptor (RyR) is a Ca(2)(+) release channel in the sarcoplasmic reticulum and plays an important role in excitation-contraction coupling in skeletal muscle. The Ca(2)(+) release through the RyR channel can be gated by two distinct modes: depolarization-induced Ca(2)(+) release (DICR) and Ca(2)(+)-induced Ca(2)(+) release (CICR). Two different RyR isoforms, RyR1 (or alpha-RyR) and RyR3 (or beta-RyR), have been found to be expressed in skeletal muscle. Most adult mammalian muscles express primarily RyR1, whereas almost equal amounts of the two RyR isoforms exist in many nonmammalian vertebrate muscles. RyR1 is believed to be responsible for both DICR and CICR, whereas RyR3 may function as the CICR channel. Recent findings demonstrate that alpha-RyR is selectively and markedly suppressed in CICR activity in frog skeletal muscle. This selective suppression of RyR1, although to a lesser extent, also was found to occur in mammalian skeletal muscle. This short review describes the biological meanings of this selective suppression and discusses physiological roles and significance of the two RyR isoforms in vertebrate skeletal muscle.
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PMID:Roles of two ryanodine receptor isoforms coexisting in skeletal muscle. 1245 93

The family of ryanodine receptor (RyR) genes encodes three highly related Ca(2+)-release channels: RyR1, RyR2 and RyR3. RyRs are known as the Ca(2+)-release channels that participate to the mechanism of excitation-contraction coupling in striated muscles, but they are also expressed in many other cell types. Actually, in several cells two or three RyR isoforms can be co-expressed and interactive feedbacks among them may be important for generation of intracellular Ca(2+) signals and regulation of specific cellular functions. Important developments have been obtained in understanding the biochemical complexity underlying the process of Ca(2+) release through RyRs. The 3-D structure of these large molecules has been obtained and some regulatory regions have been mapped within these 3-D reconstructions. Recent studies have clarified the role of protein kinases and phosphatases that, by physically interacting with RyRs, appear to play a role in the regulation of these Ca(2+)-release channels. These and other recent advancements in understanding RyR biology will be the object of this review.
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PMID:Molecular genetics of ryanodine receptors Ca2+-release channels. 1254 91

Skeletal-type E-C coupling is thought to require a direct interaction between RyR1 and the alpha(1S)-DHPR. Most available evidence suggests that the cytoplasmic II-III loop of the dihydropyridine receptor (DHPR) is the primary source of the orthograde signal. However, identification of the region(s) of RyR1 involved in bidirectional signaling with the alpha(1S)-DHPR remains elusive. To identify these regions we have designed a series of chimeric RyR cDNAs in which different segments of RyR1 were inserted into the corresponding region of RyR3 and expressed in dyspedic 1B5 myotubes. RyR3 provides a preferable background than RyR2 for defining domains essential for E-C coupling because it possesses less sequence homology to RyR1 than the RyR2 backbone used in previous studies. Our data show that two regions of RyR1 (chimera Ch-10 aa 1681-2641 and Ch-9 aa 2642-3770), were independently able to restore skeletal-type E-C coupling to RyR3. These two regions were further mapped and the critical RyR1 residues were 1924-2446 (Ch-21) and 2644-3223 (Ch-19). These results both support and refine the previous hypothesis that multiple domains of RyR1 combine to functionally interact with the DHPR during E-C coupling.
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PMID:RyR1/RyR3 chimeras reveal that multiple domains of RyR1 are involved in skeletal-type E-C coupling. 1266 74


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