Structural interaction between RYRs and DHPRs in calcium release units of cardiac and skeletal muscle cells

Protasi, Feliciano

doi:10.2741/protasi

Cited by 51 publications

(38 citation statements)

References 26 publications

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“…The structures involved in this mechanism consist of 2 membrane systems, the plasma membrane and the SR, that communicate effectively with each other through specific structures called calcium release units . These structures contain proteins that have been identified as key players in this process: the RYRs, large intracellular channels (~2260 kDa) that allow Ca 2+ release from the SR in response to the depolarization of the plasma membrane, and DHPRs, which are L-type voltage-dependent Ca 2+ channels that are present outside of the muscle cell membranes and control the opening of the RYRs (Protasi, 2002). In addition to these 2 major proteins, recent studies revealed that CaM is also involved.…”

Section: In Mammalsmentioning

confidence: 99%

Skeletal muscle calcium channel ryanodine and the development of pale, soft, and exudative meat in poultry

Paião¹,

Ferracin²,

Pedrão³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. The development of pale, soft, and exudative (PSE) breast fillet meat has become an economic burden for the poultry industry worldwide. PSE meat results in 1.0-1.5% loss in moisture and carcass weight, and a 2010 estimate of the Brazilian annual production put the economic loss due to PSE at over US$30 million. In the USA, PSE has caused an annual loss of up to US$200 million to the poultry industries. The underlying causes of the color abnormality in PSE meat are not fully understood. However, the likely physiological origin of PSE broiler meat is an excessive release of Ca 2+ promoted by a genetic mutation of the ryanodine receptor (RYR), a Ca 2+ -channel protein in the skeletal muscle sarcoplasmic reticulum. In pigs, the genetic cause of PSE meat has been identified as a point mutation in the RYR1 gene at nucleotide 1843, which causes an amino acid substitution (Arg615 to Cys615) in the RYR. This mutation leads to an alteration in Ca 2+ homeostasis, hypermetabolism, intense muscle contraction, and malignant hyperthermia in pigs susceptible to porcine stress syndrome. An understanding of this process represents the basis for breeding strategies aimed at eliminating the RYR1 mutation from global pig populations, a strategy that the poultry industry intends to emulate. The aim of this study was to review the subject, with an emphasis on the most recent developments in the field.

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Section: In Mammalsmentioning

confidence: 99%

Skeletal muscle calcium channel ryanodine and the development of pale, soft, and exudative meat in poultry

Paião¹,

Ferracin²,

Pedrão³

et al. 2013

Genet. Mol. Res.

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“…In addition to functional coupling of the DHPR and RyR1, structural coupling of these two proteins has been suggested from freeze-fracture studies of the plasma membrane, which reveal that DHPRs occur in "tetrads," groups of four intramembranous particles that are arranged in ordered arrays (Franzini-Armstrong and Kish, 1995;Beam and Franzini-Armstrong, 1997;Protasi, 2002). The individual DHPRs within a tetrad are located in exact correspondence to the four subunits of RyR1 (Franzini-Armstrong and Kish, 1995;Block et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Accessibility of Targeted DHPR Sites to Streptavidin and Functional Effects of Binding on EC Coupling

Lorenzon¹,

Beam²

2007

J Cell Biol

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In skeletal muscle, the dihydropyridine receptor (DHPR) in the plasma membrane (PM) serves as a Ca 2+ channel and as the voltage sensor for excitation-contraction (EC coupling), triggering Ca 2+ release via the type 1 ryanodine receptor (RyR1) in the sarcoplasmic reticulum (SR) membrane. In addition to being functionally linked, these two proteins are also structurally linked to one another, but the identity of these links remains unknown. As an approach to address this issue, we have expressed DHPR α 1S or β 1a subunits, with a biotin acceptor domain fused to targeted sites, in myotubes null for the corresponding, endogenous DHPR subunit. After saponin permeabilization, the ‫-06ف‬kD streptavidin molecule had access to the β 1a N and C termini and to the α 1S N terminus and proximal II-III loop (residues 671-686). Steptavidin also had access to these sites after injection into living myotubes. However, sites of the α 1S C terminus were either inaccessible or conditionally accessible in saponinpermeabilized myotubes, suggesting that these C-terminal regions may exist in conformations that are occluded by other proteins in PM/SR junction (e.g., RyR1). The binding of injected streptavidin to the β 1a N or C terminus, or to the α 1S N terminus, had no effect on electrically evoked contractions. By contrast, binding of streptavidin to the proximal α 1S II-III loop abolished such contractions, without affecting agonist-induced Ca 2+ release via RyR1. Moreover, the block of EC coupling did not appear to result from global distortion of the DHPR and supports the hypothesis that conformational changes of the α 1S II-III loop are necessary for EC coupling in skeletal muscle.

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“…RyR1 and its protein-binding partners assemble a tightly regulated macromolecular complex within the T-tubule-SR junctions termed "Ca 2ϩ release units" (CRUs). A prominent feature of the CRU is a physical interaction between the DHPR and RyR1 that permits precise alignment of DHPR tetrads over every other RyR1 (Protasi, 2002), an arrangement that is essential for engaging bidirectional signaling between the DHPR and RyR1. Thus, the ultrastructural organization of the CRU proteins is tightly linked to precise positive and negative regulation between DHPR and RyR1 Ca 2ϩ channels (Sheridan et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Functional and Biochemical Properties of Ryanodine Receptor Type 1 Channels from Heterozygous R163C Malignant Hyperthermia-Susceptible Mice

et al. 2010

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ABSTRACT3 H]Ry receptor occupancy; 3) comparatively higher channel activity, even in reducing glutathione buffer; 4) enhanced RyR1 activity both at 25 and 37°C; and 5) elevated cytoplasmic [Ca 2ϩ ] rest . R163C channels are inherently more active than WT channels, a functional impairment that cannot be reversed by dephosphorylation with protein phosphatase. Dysregulated R163C channels produce a more overt phenotype in myotubes than in adult fibers in the absence of triggering agents, suggesting tighter negative regulation of R163C-RyR1 within the Ca 2ϩ release unit of adult fibers.

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Structural interaction between RYRs and DHPRs in calcium release units of cardiac and skeletal muscle cells

Cited by 51 publications

References 26 publications

Skeletal muscle calcium channel ryanodine and the development of pale, soft, and exudative meat in poultry

Skeletal muscle calcium channel ryanodine and the development of pale, soft, and exudative meat in poultry

Accessibility of Targeted DHPR Sites to Streptavidin and Functional Effects of Binding on EC Coupling

Functional and Biochemical Properties of Ryanodine Receptor Type 1 Channels from Heterozygous R163C Malignant Hyperthermia-Susceptible Mice

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