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Journal of Agricultural and Food... Mar 2023The world's hunger is continuously rising due to conflicts, climate change, pandemics (such as the recent COVID-19), and crop pests and diseases. It is widely accepted... (Review)
Review
The world's hunger is continuously rising due to conflicts, climate change, pandemics (such as the recent COVID-19), and crop pests and diseases. It is widely accepted that zero hunger is impossible without using agrochemicals to control crop pests and diseases. Diamide insecticides are one of the widely used green insecticides developed in recent years and play important roles in controlling lepidopteran pests. Currently, eight diamine insecticides have been commercialized, which target the insect ryanodine receptors. This review summarizes the development and optimization processes of diamide derivatives acting as ryanodine receptor activators. The review also discusses pest resistance to diamide derivatives and possible solutions to overcome the limitations posed by the resistance. Thus, with reference to structural biology, this study provides an impetus for designing and developing diamide insecticides with improved insecticidal activities.
Topics: Animals; Moths; Insecticides; Ryanodine Receptor Calcium Release Channel; Diamide; COVID-19; ortho-Aminobenzoates
PubMed: 36791236
DOI: 10.1021/acs.jafc.2c08414 -
EMBO Reports May 2020Ryanodine receptor 1 (RyR1) mediates excitation-contraction coupling by releasing Ca from sarcoplasmic reticulum (SR) to the cytoplasm of skeletal muscle cells. RyR1...
Ryanodine receptor 1 (RyR1) mediates excitation-contraction coupling by releasing Ca from sarcoplasmic reticulum (SR) to the cytoplasm of skeletal muscle cells. RyR1 activation is regulated by several proteins from both the cytoplasm and lumen of the SR. Here, we report the structure of RyR1 from native SR membranes in closed and open states. Compared to the previously reported structures of purified RyR1, our structure reveals helix-like densities traversing the bilayer approximately 5 nm from the RyR1 transmembrane domain and sarcoplasmic extensions linking RyR1 to a putative calsequestrin network. We document the primary conformation of RyR1 in situ and its structural variations. The activation of RyR1 is associated with changes in membrane curvature and movement in the sarcoplasmic extensions. Our results provide structural insight into the mechanism of RyR1 in its native environment.
Topics: Animals; Calcium; Cytoplasm; Muscle Fibers, Skeletal; Muscle, Skeletal; Rabbits; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum
PubMed: 32147968
DOI: 10.15252/embr.201949891 -
Trends in Endocrinology and Metabolism:... Aug 2019Abnormal chemical reactions in hyperglycemia alter normal metabolic processes in diabetes, which is a key process in the production of reactive carbonyls species (RCS).... (Review)
Review
Abnormal chemical reactions in hyperglycemia alter normal metabolic processes in diabetes, which is a key process in the production of reactive carbonyls species (RCS). Increasing the concentration of RCS may result in carbonyl/oxidative stress in both the diabetic heart and lung. Ryanodine receptors (RyRs) not only play a key role in heart contraction, including rhythmic contraction and relaxation of the heart, but they are also important for controlling the airway smooth muscle. RCS modifies RyRs, resulting in RyRs dysfunction, which is involved in important mechanisms in diabetic complications. Very little is known about the mechanistic relationship between the heart and lung in diabetes. This review highlights new findings on the pathophysiological mechanisms and discusses potential approaches to treatment for these complications.
Topics: Animals; Diabetes Complications; Humans; Lung; Myocardium; Ryanodine Receptor Calcium Release Channel
PubMed: 31253519
DOI: 10.1016/j.tem.2019.05.005 -
Journal of Agricultural and Food... Dec 2020Photoresponsive ligands are powerful tool compounds for studying receptor function with spatiotemporal resolution. However, to the best of our knowledge, such a ligand... (Review)
Review
Photoresponsive ligands are powerful tool compounds for studying receptor function with spatiotemporal resolution. However, to the best of our knowledge, such a ligand is not available for the ryanodine receptor (RyR). Herein, we present a photochromic ligand (PCL) for insect RyR by decorating chlorantraniliprole (CHL) with photoswitchable azobenzene (AB). We demonstrated that one potent ligand, named ABCHL13, shows light-induced reversible trans-cis isomerization and 3.5-fold insecticidal activity decrease toward oriental armyworm () after UV-light irradiation, that is, -ABCH13 has higher activity than the -ABCH13. ABCHL13 enables optical control over intracellular Ca release in dorsal unpaired median (DUM) neurons of and American cockroach () and cardiac function of . Our results provide a first photopharmacological toolkit that is applicable to light-dependent regulation of RyR and heart beating.
Topics: Animals; Azo Compounds; Calcium Channel Blockers; Diamide; Insect Proteins; Insecticides; Isomerism; Ligands; Moths; Periplaneta; Ryanodine Receptor Calcium Release Channel; Structure-Activity Relationship; Ultraviolet Rays
PubMed: 33252227
DOI: 10.1021/acs.jafc.0c03272 -
Cardiac Electrophysiology Clinics Sep 2023Calcium release deficiency syndrome (CRDS) is a newly described form of inherited arrhythmia caused by damaging loss-of-function variants in the cardiac ryanodine... (Review)
Review
Calcium release deficiency syndrome (CRDS) is a newly described form of inherited arrhythmia caused by damaging loss-of-function variants in the cardiac ryanodine receptor (RyR2). Unlike the prototypical RyR2 gain-of-function channelopathy, known as catecholaminergic polymorphic ventricular tachycardia, patients with CRDS are predisposed to sudden death usually in the absence of any electrical abnormalities at rest or during stress electrocardiography. This makes diagnosis incredibly challenging, however, an invasive electrophysiologic test appears to be effective in unmasking the phenotype, called the long-burst, long-pause, short-coupled ventricular extra-stimulus protocol. Optimal therapies for patients with CRDS remain unestablished, although flecainide appears to be a promising candidate drug.
Topics: Humans; Ryanodine Receptor Calcium Release Channel; Calcium; Electrocardiography; Tachycardia, Ventricular; Flecainide; Mutation
PubMed: 37558302
DOI: 10.1016/j.ccep.2023.05.003 -
Biochemical Pharmacology Jun 2022Inherited arrhythmias are the leading causes for cardiac arrest and sudden cardiac death (SCD). Other than ion channel mutations, inherited arrhythmias including... (Review)
Review
Inherited arrhythmias are the leading causes for cardiac arrest and sudden cardiac death (SCD). Other than ion channel mutations, inherited arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), idiopathic ventricular fibrillation (IVF) and arrhythmogenic right ventricular cardiomyopathy (ARVC/D) may also be instigated by genetic mutations of sarcoplasmic reticulum (SR) proteins, including ryanodine receptor type-2 (RyR2), calsequestrin 2, SR Ca-ATPase type-2a (SERCA2a) and phospholamban. In cardiomyocytes, Ca is an essential ion in addition to Na and K ions with vital roles in arrhythmogenesis. SR plays a critical role in the maintenance of Ca homeostasis which can be disrupted by mutations in SR Ca regulatory proteins or abnormal SR-intracellular organelle interaction. Early afterdepolarizations, delayed afterdepolarizations and reentry are three primary mechanisms contributing to arrhythmias elicited by SR Ca dysregulation in cardiomyocytes. In this review, we will aim to summarize normal SR Ca regulation in cardiomyocytes, mechanisms of how Ca triggers arrhythmias and involvements of SR gene mutations in inherited arrhythmias as well as the possible arrhythmogenic effects of these mutations.
Topics: Arrhythmias, Cardiac; Calcium; Humans; Mutation; Myocytes, Cardiac; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Tachycardia, Ventricular
PubMed: 35490731
DOI: 10.1016/j.bcp.2022.115059 -
Protein Science : a Publication of the... Jan 2017Signal transduction by the ryanodine receptor (RyR) is essential in many excitable cells including all striated contractile cells and some types of neurons. While its... (Review)
Review
Signal transduction by the ryanodine receptor (RyR) is essential in many excitable cells including all striated contractile cells and some types of neurons. While its transmembrane domain is a classic tetrameric, six-transmembrane cation channel, the cytoplasmic domain is uniquely large and complex, hosting a multiplicity of specialized domains. The overall outline and substructure readily recognizable by electron microscopy make RyR a geometrically well-behaved specimen. Hence, for the last two decades, the 3D structural study of the RyR has tracked closely the technological advances in electron microscopy, cryo-electron microscopy (cryoEM), and computerized 3D reconstruction. This review summarizes the progress in the structural determination of RyR by cryoEM and, bearing in mind the leap in resolution provided by the recent implementation of direct electron detection, analyzes the first near-atomic structures of RyR. These reveal a complex orchestration of domains controlling the channel's function, and help to understand how this could break down as a consequence of disease-causing mutations.
Topics: Animals; Cryoelectron Microscopy; Humans; Imaging, Three-Dimensional; Protein Domains; Ryanodine Receptor Calcium Release Channel
PubMed: 27671094
DOI: 10.1002/pro.3052 -
Expert Opinion on Therapeutic Targets 2023Recent neuroscience breakthroughs have shed light on the sophisticated relationship between calcium channelopathies and movement disorders, exposing a previously... (Review)
Review
INTRODUCTION
Recent neuroscience breakthroughs have shed light on the sophisticated relationship between calcium channelopathies and movement disorders, exposing a previously undiscovered tale focusing on the Ryanodine Receptor (RyR) and the Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA). Calcium signaling mainly orchestrates neural communication, which regulates synaptic transmission and total network activity. It has been determined that RyR play a significant role in managing neuronal functions, most notably in releasing intracellular calcium from the endoplasmic reticulum.
AREAS COVERED
It highlights the involvement of calcium channels such as RyR and SERCA in physiological and pathophysiological conditions.
EXPERT OPINION
Links between RyR and SERCA activity dysregulation, aberrant calcium levels, motor and cognitive dysfunction have brought attention to the importance of RyR and SERCA modulation in neurodegenerative disorders. Understanding the obscure function of these proteins will open up new therapeutic possibilities to address the underlying causes of neurodegenerative diseases. The unreported RyR and SERCA narrative broadens the understanding of calcium channelopathies in movement disorders and calls for more research into cutting-edge therapeutic approaches.
Topics: Humans; Ryanodine Receptor Calcium Release Channel; Calcium; Calcium Signaling; Channelopathies; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Endoplasmic Reticulum; Neurodegenerative Diseases; Movement Disorders
PubMed: 37971192
DOI: 10.1080/14728222.2023.2277863 -
Current Opinion in Pharmacology Apr 2023Type 1 ryanodine receptor (RyR1) is an intracellular Ca release channel on the sarcoplasmic reticulum of skeletal muscle, and it plays a central role in... (Review)
Review
Type 1 ryanodine receptor (RyR1) is an intracellular Ca release channel on the sarcoplasmic reticulum of skeletal muscle, and it plays a central role in excitation-contraction (E-C) coupling. Mutations in RyR1 are implicated in various muscle diseases including malignant hyperthermia, central core disease, and myopathies. Currently, no specific treatment exists for most of these diseases. Recently, high-throughput screening (HTS) assays have been developed for identifying potential candidates for treating RyR-related muscle diseases. Currently, two different methods, namely a FRET-based assay and an endoplasmic reticulum Ca-based assay, are available. These assays identified several compounds as novel RyR1 inhibitors. In addition, the development of a reconstituted platform permitted HTS assays for E-C coupling modulators. In this review, we will focus on recent progress in HTS assays and discuss future perspectives of these promising approaches.
Topics: Humans; Ryanodine Receptor Calcium Release Channel; Muscular Diseases; Calcium Signaling; Muscle, Skeletal; Drug Development; Calcium; Mutation
PubMed: 36842386
DOI: 10.1016/j.coph.2023.102356 -
Frontiers in Immunology 2023Mast cell (MC) activation is implicated in the pathogenesis of multiple immunodysregulatory skin disorders. Activation of an IgE-independent pseudo-allergic route has...
Mast cell (MC) activation is implicated in the pathogenesis of multiple immunodysregulatory skin disorders. Activation of an IgE-independent pseudo-allergic route has been recently found to be mainly mediated Mas-Related G protein-coupled receptor X2 (MRGPRX2). Ryanodine receptor (RYR) regulates intracellular calcium liberation. Calcium mobilization is critical in the regulation of MC functional programs. However, the role of RYR in MRGPRX2-mediated pseudo-allergic skin reaction has not been fully addressed. To study the role of RYR , we established a murine skin pseudo-allergic reaction model. RYR inhibitor attenuated MRGPRX2 ligand substance P (SP)-induced vascular permeability and neutrophil recruitment. Then, we confirmed the role of RYR in an MC line (LAD2 cells) and primary human skin-derived MCs. In LAD2 cells, RYR inhibitor pretreatment dampened MC degranulation (detected by β-hexosaminidase retlease), calcium mobilization, IL-13, TNF-α, CCL-1, CCL-2 mRNA, and protein expression activated by MRGPRX2 ligands, namely, compound 48/80 (c48/80) and SP. Moreover, the inhibition effect of c48/80 by RYR inhibitor was verified in skin MCs. After the confirmation of RYR2 and RYR3 expression, the isoforms were silenced by siRNA-mediated knockdown. MRGPRX2-induced LAD2 cell exocytosis and cytokine generation were substantially inhibited by RYR3 knockdown, while RYR2 had less contribution. Collectively, our finding suggests that RYR activation contributes to MRGPRX2-triggered pseudo-allergic dermatitis, and provides a potential approach for MRGPRX2-mediated disorders.
Topics: Humans; Animals; Mice; Calcium; Ryanodine; Ryanodine Receptor Calcium Release Channel; Mast Cells; Receptors, G-Protein-Coupled; Dermatitis, Atopic; Nerve Tissue Proteins; Receptors, Neuropeptide
PubMed: 37404822
DOI: 10.3389/fimmu.2023.1207249