genes significantly affected in female MDD subjects
genes significantly affected in female MDD subjects
Positive relationships between RYR2 and other components at different levels (count: 0)
Positive relationship network of RYR2 in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network.
If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
Accordingly, the relationship is marked with dot line.
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3. The network is generated using Cytoscape Web
Negative relationships between RYR2 and MDD (count: 0)
Negative relationships between RYR2 and other components at different levels (count: 0)
positive regulation of ryanodine-sensitive calcium-release channel activity by adrenergic receptor signaling pathway involved in positive regulation of cardiac muscle contraction
Ca2+ that enters the cell from the outside is a principal so......
Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM).More...
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an......
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVD/C. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death.More...
Hypertrophic cardiomyopathy (HCM) is a primary myocardial di......
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myofibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in 11 genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myofilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction.More...
Dilated cardiomyopathy (DCM) is a heart muscle disease chara......
Dilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac death from ventricular arrhythmia. Genetically inherited forms of DCM (familial DCM) have been identified in 25-35% of patients presenting with this disease, and the inherited gene defects are an important cause of familial DCM. The pathophysiology may be separated into two categories: defects in force generation and defects in force transmission. In cases where an underlying pathology cannot be identified, the patient is diagnosed with an idiopathic DCM. Current hypotheses regarding causes of idiopathic DCM focus on chronic viral myocarditis and/or on autoimmune abnormalities. Viral myocarditis may progress to an autoimmune phase and then to progressive cardiac dilatation. Antibodies to the beta1-adrenergic receptor (beta1AR), which are detected in a substantial number of patients with idiopathic DCM, may increase the concentration of intracellular cAMP and intracellular Ca2+, a condition often leading to a transient hyper-performance of the heart followed by depressed heart function and heart failure.More...
Contraction of the heart is a complex process initiated by t......
Contraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation of voltage-dependent L-type Ca channels (DHP receptors) upon membrane depolarization triggers the release of Ca2+ via Ca2+ release channels (ryanodine receptors) of sarcoplasmic reticulum (SR) through a Ca2+ -induced Ca release (CICR) mechanism. Ca2+ ions released via the CICR mechanism diffuse through the cytosolic space to contractile proteins to bind to troponinC resulting in the release of inhibition induced by troponinI. The Ca2+ binding to troponinC thereby triggers the sliding of thin and thick filaments, that is, the activation of a crossbridge and subsequent cardiac force development and/or cell shortening. Recovery occurs as Ca2+ is pumped out of the cell by the Na+/Ca2+ exchanger (NCX) or is returned to the sarcoplasmic reticulum (SR) by sarco(endo)plasmic Ca2+ -ATPase (SERCA) pumps on the non-junctional region of the SR.More...
Nitric oxide (NO) has a number of important physiological ac......
Nitric oxide (NO) has a number of important physiological actions in the cardiovascular system. In the heart, NO plays role in keeping the vessels patent via vasodilation and prevention of platelet aggregation. It also plays an important role in regulating the force and rate of contraction. In vivo NO is released by shear stress of ligands that increase intracellular Ca2+ in endothelial cells. The increase intracellular Ca2+ activates nitric oxide synthase III (NOSIII) by promoting the binding of Ca/Calmodulin to the enzyme. NOSIII, which is resident in the Golgi complex, is transported together with caveolin-1 to the caveolae at the plasma membrane via vesicles. Shear stress signals via a potassium channel and the cytoskeleton, which results in tyrosine phosphorylation of specific proteins, activation of phosphatidylinositol 3-kinase, and subsequently in activation of Akt kinase. Akt activation by shear stress but also by VEGF activates NOSIII by serine phosphorylation, which increases the affinity of NOSIII for calmodulin. After agonist binding at the plasma membrane, NOSIII-activating receptors translocate to caveolae. VEGF receptor signals via its tyrosine kinase domain. Furthermore, agonist receptors activate calcium channels of the endoplasmic reticulum (ER) via phospholipase C and inositol 1,4,5-trisphosphate. This calcium flux induces binding of calmodulin to NOSIII, whereas the NOSIII-caveolin-1 interaction is disrupted. At the same time, NOSIII is translocated into the cytosol. On binding of calmodulin, NOSIII generates NO, is enhanced by the interaction with Hsp90. Once activated, NOSIII catabolizes L-arginine to NO, which diffuses out of the cell. NO stimulates guanylate (G-) cyclase and increases cGMP levels. cGMP activates cGMP-dependent protein kinase (PKG), cGMP-inhibited phosphodiesterase (PDEIII), and cGMP-stimulated phosphodiesterase (PDEII). PKG may reduce the force and rate of contraction, possibly by phosphorylating troponin I or by phosphorylating phospholamban. PDEIII is inhibited by the increases in cGMP brought about by NO. This may result in an increase in cAMP and cAMP-dependent protein kinase (PKA). PKA in turn activates Ca2+ channels, countering the effects of PKG. In contrast, cGMP may stimulate PDEII, reduce cAMP levels and PKA activity, and thereby reduce Ca2+ channel activity. Ach, acetylcholine. CAT-1, cationic amino acid transporter.More...
RYR2 related Reactome pathways (count: 0)
RYR2 related interactors from protein-protein interaction data in HPRD (count: 12)
Basic Information
Positive relationships between RYR2 and other components at different levels (count: 0)
