A brain‐specific transcript from the 3′‐terminal region of the skeletal muscle ryanodine receptor gene

Takeshima, Hiroshi; Nishimura, Seiichiro; Nishi, Miyuki; Ikeda, Michiko; Sugimoto, Tetsuo

doi:10.1016/0014-5793(93)81547-d

Cited by 52 publications

(26 citation statements)

References 28 publications

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“…In contrast, three amplified cDNA fragments were observed when RNA from brain was used as the template under the same conditions. The results are consistent with the distribution of the RyR subtype mRNAs examined previously by Northern blot and in situ hybridization analysis (Hakamata et al, 1992;Takeshima et al, 1993;Furuichi et al, 1994). The [Ca2+]i rise induced by caffeine results in contractions of cultured muscle cells from both dyspedic and control mice.…”

Section: Introductionsupporting

confidence: 91%

Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.

et al. 1995

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While subtypes 1 and 2 of the ryanodine receptor (RyR) function as intracellular Ca2+ release channels, little is known about the function of the third subtype (RyR-3), first identified in brain. Myocytes from mice homozygous for a targeted mutation in the RyR-1 gene (dyspedic mice) can now be used for a study on the function of RyR-3, which is predominantly expressed in these cells according to our reverse transcriptionpolymerase chain reaction analysis. We here demonstrate in these myocytes caffeine-, ryanodine-and adenine nucleotide-sensitive Ca>+-induced Ca2> release with -10 times lower sensitivity to Ca2+ than that of RyR-1. Although RyR-3 does not mediate excitationcontraction coupling of the skeletal muscle type, we propose that RyR-3 may induce intracellular Ca2+ release in response to a Ca2+ rise with a high threshold.

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Section: Introductionsupporting

confidence: 91%

Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.

et al. 1995

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“…Previous studies have reported that the ER retention signal is likely present within the COOH-terminal portion of RyR1 (9,53,78) or RyR2 (22), which contains transmembrane domains (TMDs). Bhat and Ma (9) reported that amino acids 4918 -4943 of RyR1, which are within TMD6 and have a consensus sequence with the IP 3 receptor and RyR2, contain a strong ER retention signal (Fig.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca²⁺-induced ATP production in cardiac H9c2 myoblasts

O‐Uchi

Jhun

Hurst

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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ϩ influx to mitochondria is an important trigger for both mitochondrial dynamics and ATP generation in various cell types, including cardiac cells. Mitochondrial Ca 2ϩ influx is mainly mediated by the mitochondrial Ca 2ϩ uniporter (MCU). Growing evidence also indicates that mitochondrial Ca 2ϩ influx mechanisms are regulated not solely by MCU but also by multiple channels/transporters. We have previously reported that skeletal muscle-type ryanodine receptor (RyR) type 1 (RyR1), which expressed at the mitochondrial inner membrane, serves as an additional Ca 2ϩ uptake pathway in cardiomyocytes. However, it is still unclear which mitochondrial Ca 2ϩ influx mechanism is the dominant regulator of mitochondrial morphology/dynamics and energetics in cardiomyocytes. To investigate the role of mitochondrial RyR1 in the regulation of mitochondrial morphology/function in cardiac cells, RyR1 was transiently or stably overexpressed in cardiac H9c2 myoblasts. We found that overexpressed RyR1 was partially localized in mitochondria as observed using both immunoblots of mitochondrial fractionation and confocal microscopy, whereas RyR2, the main RyR isoform in the cardiac sarcoplasmic reticulum, did not show any expression at mitochondria. Interestingly, overexpression of RyR1 but not MCU or RyR2 resulted in mitochondrial fragmentation. These fragmented mitochondria showed bigger and sustained mitochondrial Ca 2ϩ transients compared with basal tubular mitochondria. In addition, RyR1-overexpressing cells had a higher mitochondrial ATP concentration under basal conditions and showed more ATP production in response to cytosolic Ca 2ϩ elevation compared with nontransfected cells as observed by a matrix-targeted ATP biosensor. These results indicate that RyR1 possesses a mitochondrial targeting/retention signal and modulates mitochondrial morphology and Ca 2ϩ -induced ATP production in cardiac H9c2 myoblasts. fluorescence resonance energy transfer; mitochondrial Ca 2ϩ uniporter; mitochondria; mitochondrial morphology; ryanodine receptor type 1 MITOCHONDRIAL Ca 2ϩ is critical for the regulation of various cellular functions, including energy metabolism, ROS generation, spatiotemporal dynamics of Ca 2ϩ signaling, and cell growth/development and death (11,18,23). Historically, Ca 2ϩ was found to be accumulated by mitochondria over 5 decades ago (for reviews, see Refs. 24, 64, and 69), and, shortly thereafter, it was also recognized that Ca 2ϩ stimulates the oxidative phosphorylation [tricarboxylic acid (TCA) cycle] and electron transport chain activity, which results in the stimulation of ATP synthesis (for a review, see Ref. 23). Additionally, the coexistence of mitochondrial dysfunction and loss of cellular Ca 2ϩ homeostasis are frequently observed in various cardiovascular diseases, but it is still not clear how altered mitochondrial Ca 2ϩ handing and/or mitochondrial dysfunction are involved in the pathogenesis of each different disease setting (23,33,56).Although the basic functional and pharmacological properties of mitochondrial ...

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“…RyR expressed in heterologous cells is localized to the ER membrane, suggesting that the signal(s) responsible for intracellular localization of RyR is present within its primary amino acid sequence (3,9,10). Using fusion proteins of RyR and green fluorescent protein (GFP) expressed in CHO cells, we have observed that the C-terminal portion of RyR contains sequence(s) responsible for its ER localization (3).…”

Section: Cule (Icam) Various Fragments Of Ryr and Green Fluorescentmentioning

confidence: 99%

The Transmembrane Segment of Ryanodine Receptor Contains an Intracellular Membrane Retention Signal for Ca2+ Release Channel

Ma¹

2002

Journal of Biological Chemistry

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The ryanodine receptor (RyR) is a large homotetrameric protein with a hydrophobic domain at the Cterminal end that resides in the endoplasmic reticulum (ER) or sarcoplasmic reticulum membrane and forms the conduction pore of a Ca 2؉ release channel. Our previous studies showed that RyR expressed in heterologous cells localized to the ER membrane. Confocal microscopic imaging indicated that the ER retention signal is likely present within the C-terminal portion of RyR, a region that contains four putative transmembrane segments. To identify the amino acid sequence responsible for ER retention of RyR, we expressed fusion proteins containing intercellular adhesion molecule (

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A brain‐specific transcript from the 3′‐terminal region of the skeletal muscle ryanodine receptor gene

Cited by 52 publications

References 28 publications

Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.

Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.

Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca²⁺-induced ATP production in cardiac H9c2 myoblasts

The Transmembrane Segment of Ryanodine Receptor Contains an Intracellular Membrane Retention Signal for Ca2+ Release Channel

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A brain‐specific transcript from the 3′‐terminal region of the skeletal muscle ryanodine receptor gene

Cited by 52 publications

References 28 publications

Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.

Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.

Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca2+-induced ATP production in cardiac H9c2 myoblasts

The Transmembrane Segment of Ryanodine Receptor Contains an Intracellular Membrane Retention Signal for Ca2+ Release Channel

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Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca²⁺-induced ATP production in cardiac H9c2 myoblasts