ライフサイエンスコーパス: RyR3

1 nodine receptors type 1 and type 3 (RyR1 and RyR3).

2 ryanodine receptor/calcium release channel (RyR3).

3 natal muscles contain two isoforms (RyR1 and RyR3).

4 erase (GST) fused to its amino terminus (GST-RyR3).

5 Reduced RyR1 was greater than that of RyR3.

6 for RyR1 and does not express either RyR1 or RyR3.

7 n as diversity region 2) that is absent from RyR3.

8 ells independently expressing either RyR1 or RyR3.

9 L3873Q/Q3874K) imparted 4-CmC sensitivity to RyR3.

10 ble to restore skeletal-type E-C coupling to RyR3.

11 382) that each imparted 4-CmC sensitivity to RyR3.

12 ender depolarization-induced Ca2+ release to RyR3.

13 fic isoform of the ryanodine Ca(2+) channel, RyR3.

14 taneous release events generated by RyR1 and RyR3.

15 reticulum Ca(2+) release channels, RyR1 and RyR3.

16 nes expressed not only RYR1 or RYR2 but also RYR3.

17 -shaped cytoplasmic region of homotetrameric RyR3.

18 Under reducing conditions, RyR1 and RyR3 activities are inhibited with a similar affinity at

19 In muscles containing RyR1 as well as RyR3, additional feet are located in lateral parajunctio

20 airway smooth muscle increases, RyR1 and/or RyR3 also mediate the calcium response and thus bronchoc

21 Surprisingly, we found that RyR3, although incapable of supporting EC coupling or te

22 a(2+)-induced Ca(2+) release (CICR) and that RyR3 amplifies RyR1-mediated CICR in neonatal skeletal m

23 bility to produce sparks, and they also lose RyR3, an isoform abundant in spark-producing skeletal mu

24 le, some muscles also express high levels of RyR3, an isoform with a wide tissue distribution.

25 Biochemical content of RyR3 and content of parajunctional feet are highly corre

26 re inserted into the corresponding region of RyR3 and expressed in dyspedic 1B5 myotubes.

27 3D reconstructions of both recombinant RyR3 and GST-RyR3 appeared very similar to that of the n

28 Purified recombinant RyR3 and GST-RyR3 proteins exhibited high-affinity [(3)H

29 Comparison of the 3D reconstructions of RyR3 and GST-RyR3 revealed that the GST domains and, hen

30 trations (<1 microM), CaM activates RyR1 and RyR3 and inhibits RyR2.

31 the specific Ca(2+) release channel subtypes RyR3 and IP(3)R2 in patches along OP processes.

32 examine the local Ca(2+) release behavior of RyR3 and RyR1 in a homologous cellular system.

33 in HEK293 cells, one encoding the wild-type RyR3 and the other encoding RyR3 containing glutathione

34 lly affect CaM binding and CaM regulation of RyR3 and those of the two other isoforms.

35 nstructions of both recombinant RyR3 and GST-RyR3 appeared very similar to that of the native RyR3 pu

36 1 (RyR1) and type 2 (RyR2), but not type 3 (RyR3), are efficiently activated by 4-chloro-m-cresol (4

37 e of e-c coupling in muscle cells containing RyR3 but lacking RyR1 (see the accompanying report, ).

38 lts thus indicate that both the RYR1 and the RYR3, but not the RYR2, may be targets for dantrolene in

39 we report that the regulation of recombinant RyR3 by CaM is sensitive to redox regulation.

40 Substitution of the RyR3 C terminus into RyR1 disrupted 4-CmC sensitivity in

41 Such functional interplay between RyR1 and RyR3 can serve important roles in Ca(2+) signaling of ce

42 r Cs(+) in bilayer lipid membranes, 74 of 88 RyR3 channels exhibited pronounced subconductance behavi

43 ting and conductance level of single RyR1 or RyR3 channels when studied in lipid bilayers.

44 ic enhancement of EC coupling restored by an RyR3 chimera containing amino acids 1,681-3,770 of RyR1.

45 in vivo, we have studied the ability of RyR1/RyR3 chimera to rescue skeletal EC coupling in dyspedic

46 f DHPR into tetrad arrays by expressing RyR1-RyR3 chimerae in dyspedic myotubes.

47 ating activation by 4-CmC, we expressed RyR1-RyR3 chimeric proteins in dyspedic 1B5 myotubes and then

48 s trigger Ca(2+), and a slave parajunctional RyR3 cohort.

49 RyR1-RyR3 constructs bearing RyR1 residues 1-1681 restored wi

50 ng the wild-type RyR3 and the other encoding RyR3 containing glutathione S-transferase (GST) fused to

51 (containing both RyR1 and RyR3 isoforms) and RyR3-/- (containing only RyR1) myotubes in the presence

52 Mutagenesis studies demonstrate that RyR3 contains a single conserved CaM binding site.

53 ) and Lys(4021)) that, when mutated to their RyR3 counterparts (Leu(3873) and Gln(3874)), abolished 4

54 and RyR2, but divergent in RyR3, with their RyR3 counterparts reduced 4-CmC sensitivity to the same

55 ranscript levels increased, whereas those of RyR3 decreased after T cell activation.

56 l muscles of adult mice expressing exogenous RyR3, demonstrated as immunoreactivity at triad junction

57 The reconstructions of RyR3 determined under "open" and "closed" conditions wer

58 Intact myotubes expressing RyR3 did not, however, respond to K(+) depolarization.

59 ype excitation-contraction coupling, whereas RyR3 did not.

60 ve of a link to RyRs, those transfected with RyR3 do not.

61 Because RyR3 does not contact voltage sensors, their opening was

62 hese functional differences between RyR1 and RyR3 expressed in a mammalian muscle context may reflect

63 e to caffeine and CMC but were never seen in RyR3-expressing 1B5 cells.

64 ricted "Ca(2+) spark"-like events, events in RyR3-expressing myotubes were larger in amplitude and du

65 Although RyR3-expressing myotubes were more sensitive to caffeine

66 spatially more extensive than those seen in RyR3-expressing myotubes; however, when analysis was lim

67 This indicates that RyR3 fails to link to DHPRs in a specific manner.

68 be, in part, the result of lower affinity of RyR3 for FKBP12.

69 Recombinant type 3 ryanodine receptor (RyR3) has been purified in quantities sufficient for str

70 However, studies on mammalian RyR3 have been difficult because of low expression level

71 itution of the C-terminal third of RyR1 into RyR3 imparted 4-CmC sensitivity to the resulting chimera

72 amplicon system, we expressed either RyR1 or RyR3 in 1B5 RyR-deficient myotubes.

73 We studied the participation of RyR3 in calcium release in wild type (containing both Ry

74 Moreover, RyR1 and/or RyR3 in mouse airway smooth muscle also appear to mediat

75 e supports the hypothesis that activation of RyR3 in skeletal muscle cells must be indirect and provi

76 We have explored the structural role of RyR3 in the assembly of CRUs in 1B5 cells independently

77 RyR3 in the presence of reduced glutathione binds CaM wi

78 ween the Ca(2+) release behavior of RyR1 and RyR3 in this homologous expression system.

79 With the co-presence of RyR1 and RyR3 in wild-type cells, unmitigated radial CICR propaga

80 y inhibited by dantrolene, and the extent of RYR3 inhibition was similar to that displayed by the RYR

81 nd skeletal muscle (RyR1) receptor isoforms, RyR3 is a homotetrameric complex comprising two main com

82 t IpTxa can interact with both RyRs and that RyR3 is functional in myotubes and it can amplify the ca

83 he periphery near the cell membrane, whereas RyR3 is more centrally localized.

84 1B5 myotubes is activated by 4-CmC, whereas RyR3 is not.

85 Because it applies whether RyR3 is present or not, it is this exclusion by voltage

86 In contrast, the role of RyR3 is unknown.

87 By comparison, the RYR3 isoform expressed in HEK-293 cells was significantl

88 operated sparks phenotype is specific to the RyR3 isoform.

89 yR3 KO myotubes concluded that both RyR1 and RyR3 isoforms participated in Ca2+-dependent Ca2+ releas

90 lease in wild type (containing both RyR1 and RyR3 isoforms) and RyR3-/- (containing only RyR1) myotub

91 ibed to the absence of ryanodine receptor 3 (RyR3) isoforms in adult mammalian muscle.

92 s of wild-type or ryanodine receptor type 3 (RyR3) knockout mice.

93 In RyR3-knockout myotubes (655 events, 83 cells) the amplit

94 on under voltage clamp of both wild-type and RyR3-knockout myotubes produced substantial Ca2+ release

95 events were detected in intact wild-type and RyR3-knockout myotubes.

96 e receptor type 3 (RyR3) KO, and double RyR1/RyR3 KO mice under voltage clamp with simultaneous monit

97 ression in RyR3 KO, RyR1 KO, and double RyR1/RyR3 KO myotubes concluded that both RyR1 and RyR3 isofo

98 A comparison of beta2a overexpression in RyR3 KO, RyR1 KO, and double RyR1/RyR3 KO myotubes concl

99 type 1 (RyR1) KO, ryanodine receptor type 3 (RyR3) KO, and double RyR1/RyR3 KO mice under voltage cla

100 e 1 and type 3 ryanodine receptors (RyR1 and RyR3) located in the sarcoplasmic reticulum membrane.

101 ces in gating behavior exhibited by RyR1 and RyR3 may be, in part, the result of lower affinity of Ry

102 RyR2 and RyR3 mRNAs were upregulated, RyR2 was S-glutathionylated

103 In addition, our data indicate that when RyR3-/- myotubes are voltage-clamped, the effect of IpTx

104 rom atrial muscle to the SAN center: RYR2 to RYR3, Na(v)1.5 to Na(v)1.1, Ca(v)1.2 to Ca(v)1.3 and K(v

105 es expressed twice the RyR2 but only 65% the RyR3 of arterioles and neither vessel expressed RyR1.

106 Purified recombinant RyR3 and GST-RyR3 proteins exhibited high-affinity [(3)H]ryanodine bi

107 RyR3 provides a preferable background than RyR2 for defi

108 appeared very similar to that of the native RyR3 purified from bovine diaphragm.

109 well developed transverse tubule system, the RyR3 reinforcement of CICR seems to ensure a robust, uni

110 R, and the role of the transiently expressed RyR3 remains elusive.

111 , a significant difference between RyR1- and RyR3-rescued junctions is revealed by freeze fracture.

112 muscle and brain isoforms of RyRs (RyR1 and RyR3, respectively).

113 Expression of RyR3 restored caffeine-sensitive, global Ca(2+) release

114 on of the 3D reconstructions of RyR3 and GST-RyR3 revealed that the GST domains and, hence, the amino

115 II; however, alphaKAP, beta2 CaMK-II and the RyR3 ryanodine receptor were also necessary for full CaM

116 addition, substitution of the corresponding RyR3 sequence into positions 4007-4180 of RyR1 disrupted

117 d a complementary set of chimeras containing RyR3 substitutions in RyR1.

118 ed that isolated ICC expressed both RyR2 and RyR3 subtypes.

119 domains and, hence, the amino termini of the RyR3 subunits are located in the "clamp" structures that

120 (2+) release after the induction of RYR2 and RYR3 that occurred after treatment with stromal cell-der

121 lf failed to restore skeletal EC coupling to RyR3, the addition of the D2 region resulted in a dramat

122 In myotubes lacking RyR3, the peripheral VICR component is unaffected, and R

123 nds RyR3 with reduced affinity but activates RyR3 to a greater extent.

124 nd (iii) a form of retrograde signaling from RyR3 to the DHPR occurs in the absence of direct protein

125 n, mutation of the corresponding residues in RyR3 to their RyR1 counterparts (L3873Q/Q3874K) imparted

126 RyR1, RyR2, and RyR3 transcripts were detected in human T cells.

127 Western blot analysis revealed that RyR1- or RyR3-transduced cells expressed the appropriate RyR isof

128 Purification of GST-RyR3 was achieved by affinity chromatography by using gl

129 RyR3 was purified from detergent-solubilized transfected

130 [(3)H]ryanodine binding to RyR1 or RyR3 was significantly increased in the presence of IpTx

131 Type 3 RYR (RYR3) was not detected in PBMCs.

132 RyR3, which disappears in adult muscle, is not involved

133 In contrast, inhibiting only RyR1 and RyR3 with 25 microM dantrolene attenuated these response

134 reducing and oxidizing conditions, CaM binds RyR3 with reduced affinity but activates RyR3 to a great

135 ity of the isoforms, detailed comparisons of RyR3 with RyR1 showed one region of highly significant d

136 rved between RyR1 and RyR2, but divergent in RyR3, with their RyR3 counterparts reduced 4-CmC sensiti