The Experts below are selected from a list of 381231 Experts worldwide ranked by ideXlab platform
D. G. Stephenson - One of the best experts on this subject based on the ideXlab platform.
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Phosphate transport into the sarcoplasmic Reticulum of skinned fibres from rat skeletal muscle
Journal of Muscle Research and Cell Motility, 1997Co-Authors: M W Fryer, Jan M. West, D. G. StephensonAbstract:The rate, magnitude and pharmacology of inorganic phosphate (Pi) transport into the sarcoplasmic Reticulum were estimated in single, mechanically skinned skeletal muscle fibres of the rat. This was done, indirectly, by using a technique that measured the total Ca2+ content of the sarcoplasmic Reticulum and by taking advantage of the 1:1 stoichiometry of Ca2+ and Pi transport into the sarcoplasmic Reticulum lumen during Ca--Pi precipitation- induced Ca2+ loading. The apparent rate of Pi entry into the sarcoplasmic Reticulum increased with increasing myoplasmic [Pi] in the 10 mm--50 mm range at a fixed, resting myoplasmic pCa of 7.15, as judged by the increase in the rate of Ca--Pi precipitation-induced sarcoplasmic Reticulum Ca2+ uptake. At 20 mm myoplasmic [Pi] the rate of Pi entry was calculated to be at least 51 μm s−1 while the amount of Pi loaded appeared to saturate at around 3.5 mm (per fibre volume). These values are approximations due to the complex kinetics of formation of different species of Ca--Pi precipitate formed under physiological conditions. Phenylphosphonic acid (PhPA, 2.5 mm inhibited Pi transport by 37% at myoplasmic pCa 6.5 and also had a small, direct inhibitory effect on the sarcoplasmic Reticulum Ca2+ pump (16%). In contrast, phosphonoformic acid (PFA, 1 mm) appeared to enhance both the degree of Pi entry and the activity of the sarcoplasmic Reticulum Ca2+ pump, results that were attributed to transport of PFA into the sarcoplasmic Reticulum lumen and its subsequent complexation with Ca2+. Thus, results from these studies indicate the presence of a Pi transporter in the sarcoplasmic Reticulum membrane of mammalian skeletal muscle fibres that is (1) active at physiological concentrations of myoplasmic Pi and Ca2+ and (2) partially inhibited by PhPA. This Pi transporter represents a link between changes in myoplasmic [Pi] and subsequent changes in sarcoplasmic Reticulum luminal [Pi]. It might therefore play a role in the delayed metabolic impairment of sarcoplasmic Reticulum Ca2+ release seen during muscle fatigue, which should occur abruptly once the Ca--Pi solubility product is exceeded in the sarcoplasmic Reticulum lumen
Marek Michalak - One of the best experts on this subject based on the ideXlab platform.
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Calcium binding chaperones of the endoplasmic Reticulum
General physiology and biophysics, 2009Co-Authors: Helen Coe, Marek MichalakAbstract:The endoplasmic Reticulum is a major Ca(2+) store of the cell that impacts many cellular processes within the cell. The endoplasmic Reticulum has roles in lipid and sterol synthesis, protein folding, post-translational modification and secretion and these functions are affected by intraluminal endoplasmic Reticulum Ca(2+). In the endoplasmic Reticulum there are several Ca(2+) buffering chaperones including calreticulin, Grp94, BiP and protein disulfide isomerase. Calreticulin is one of the major Ca(2+) binding/buffering chaperones in the endoplasmic Reticulum. It has a critical role in Ca(2+) signalling in the endoplasmic Reticulum lumen and this has significant impacts on many Ca(2+)-dependent pathways including control of transcription during embryonic development. In addition to Ca(2+) buffering, calreticulin plays important role in the correct folding and quality control of newly synthesized glycoproteins.
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Calreticulin, Ca2+, and calcineurin - signaling from the endoplasmic Reticulum.
Molecules and cells, 2004Co-Authors: Jody Groenendyk, Jeffrey M. Lynch, Marek MichalakAbstract:Calcium (Ca2+) is a universal signalling molecule involved in many aspects of cellular function. The majority of intracellular Ca2+ is stored in the endoplasmic Reticulum and once Ca2+ is released from the endoplasmic Reticulum, specific plasma membrane Ca2+ channels are activated, resulting in increased intracellular Ca2+. In the lumen of the endoplasmic Reticulum, Ca2+ is buffered by Ca2+ binding chaperones such as calreticulin. Calreticulin-deficiency is lethal in utero due to impaired cardiac development and in the absence of calreticulin, Ca2+ storage capacity within the endoplasmic Reticulum and inositol 1,4,5-trisphosphate (InsP3) receptor mediated Ca2+ release from the endoplasmic Reticulum are compromised. Over-expression of constitutively active calcineurin in the heart rescues calreticulin-deficient mice from embryonic lethality. This observation indicates that calreticulin is a key upstream regulator of calcineurin in Ca2+-signalling pathways and highlights the importance of the endoplasmic Reticulum and endoplasmic Reticulum-dependent Ca2+ homeostasis for cellular commitment and tissue development during organogenesis. Furthermore, Ca2+ handling by the endoplasmic Reticulum has profound effects on cell sensitivity to apoptosis. Signalling between calreticulin in the lumen of the endoplasmic Reticulum and calcineurin in the cytoplasm may play a role in the modulation of cell sensitivity to apoptosis and the regulation of Ca2+-dependent apoptotic pathways.
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ca2 signaling and calcium binding chaperones of the endoplasmic Reticulum
Cell Calcium, 2002Co-Authors: Marek Michalak, J Robert M Parker, Michal OpasAbstract:Abstract The endoplasmic Reticulum is a centrally located organelle which affects virtually every cellular function. Its unique luminal environment consists of Ca2+ binding chaperones, which are involved in protein folding, post-translational modification, Ca2+ storage and release, and lipid synthesis and metabolism. The environment within the lumen of the endoplasmic Reticulum has profound effects on endoplasmic Reticulum function and signaling, including apoptosis, stress responses, organogenesis, and transcriptional activity. Calreticulin, a major Ca2+ binding (storage) chaperone in the endoplasmic Reticulum, is a key component of the calreticulin/calnexin cycle which is responsible for the folding of newly synthesized proteins and glycoproteins and for quality control pathways in the endoplasmic Reticulum. The function of calreticulin, calnexin and other endoplasmic Reticulum proteins is affected by continuous fluctuations in the concentration of Ca2+ in the endoplasmic Reticulum. Thus, changes in Ca2+ concentration may play a signaling role in the lumen of the endoplasmic Reticulum as well as in the cytosol. Recent studies on calreticulin-deficient and transgenic mice have revealed that calreticulin and the endoplasmic Reticulum may be upstream regulators in the Ca2+-dependent pathways that control cellular differentiation and/or organ development.
Ann Burchell - One of the best experts on this subject based on the ideXlab platform.
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Endoplasmic Reticulum phosphate transport
Kidney international, 1996Co-Authors: Ann BurchellAbstract:Endoplasmic Reticulum phosphate transport . The major role of the liver endoplasmic Reticulum phosphate/pyrophosphate transport proteins is the regulation of blood glucose levels. The glucose-6-phosphatase enzyme is an endoplasmic Reticulum enzyme system which hydrolyzes glucose-6-phosphate to glucose and phosphate. Glucose-6-phosphatase is the terminal step of both gluconeogenesis and glycogenolysis. The glucose-6-phosphatase enzyme is a very hydrophobic membrane protein and its active site is inside the lumen of the endoplasmic Reticulum. The substrates and products of the enzyme therefore have to cross the endoplasmic Reticulum membrane. The glucose-6-phosphatase enzyme is associated with a calcium binding protein (SP). There are also transport proteins for the substrate glucose-6-phosphate (T1) and the products phosphate (T2) and glucose (T3). There appear to be at least two different liver endoplasmic Reticulum proteins that can transport phosphate. One of the proteins T2b can also transport pyrophosphate and carbamyl phosphate which are also substrates for the glucose-6-phosphatase enzyme. The metabolic regulation, genetic deficiencies, ontogeny and tissue distribution of the endoplasmic Reticulum T2 proteins will be described.
Emmanuel Culetto - One of the best experts on this subject based on the ideXlab platform.
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The ESCRT-II proteins are involved in shaping the sarcoplasmic Reticulum in C. elegans.
Journal of Cell Science, 2016Co-Authors: Christophe Lefebvre, Céline Largeau, Xavier Michelet, Cécile Fourrage, Xavier Maniere, Ivan Matic, Renaud Legouis, Emmanuel CulettoAbstract:The sarcoplasmic Reticulum is a network of tubules and cisternae localized in close association with the contractile apparatus, and regulates Ca(2+)dynamics within striated muscle cell. The sarcoplasmic Reticulum maintains its shape and organization despite repeated muscle cell contractions, through mechanisms which are still under investigation. The ESCRT complexes are essential to organize membrane subdomains and modify membrane topology in multiple cellular processes. Here, we report for the first time that ESCRT-II proteins play a role in the maintenance of sarcoplasmic Reticulum integrity inC. elegans ESCRT-II proteins colocalize with the sarcoplasmic Reticulum marker ryanodine receptor UNC-68. The localization at the sarcoplasmic Reticulum of ESCRT-II and UNC-68 are mutually dependent. Furthermore, the characterization of ESCRT-II mutants revealed a fragmentation of the sarcoplasmic Reticulum network, associated with an alteration of Ca(2+)dynamics. Our data provide evidence that ESCRT-II proteins are involved in sarcoplasmic Reticulum shaping.
M W Fryer - One of the best experts on this subject based on the ideXlab platform.
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Phosphate transport into the sarcoplasmic Reticulum of skinned fibres from rat skeletal muscle
Journal of Muscle Research and Cell Motility, 1997Co-Authors: M W Fryer, Jan M. West, D. G. StephensonAbstract:The rate, magnitude and pharmacology of inorganic phosphate (Pi) transport into the sarcoplasmic Reticulum were estimated in single, mechanically skinned skeletal muscle fibres of the rat. This was done, indirectly, by using a technique that measured the total Ca2+ content of the sarcoplasmic Reticulum and by taking advantage of the 1:1 stoichiometry of Ca2+ and Pi transport into the sarcoplasmic Reticulum lumen during Ca--Pi precipitation- induced Ca2+ loading. The apparent rate of Pi entry into the sarcoplasmic Reticulum increased with increasing myoplasmic [Pi] in the 10 mm--50 mm range at a fixed, resting myoplasmic pCa of 7.15, as judged by the increase in the rate of Ca--Pi precipitation-induced sarcoplasmic Reticulum Ca2+ uptake. At 20 mm myoplasmic [Pi] the rate of Pi entry was calculated to be at least 51 μm s−1 while the amount of Pi loaded appeared to saturate at around 3.5 mm (per fibre volume). These values are approximations due to the complex kinetics of formation of different species of Ca--Pi precipitate formed under physiological conditions. Phenylphosphonic acid (PhPA, 2.5 mm inhibited Pi transport by 37% at myoplasmic pCa 6.5 and also had a small, direct inhibitory effect on the sarcoplasmic Reticulum Ca2+ pump (16%). In contrast, phosphonoformic acid (PFA, 1 mm) appeared to enhance both the degree of Pi entry and the activity of the sarcoplasmic Reticulum Ca2+ pump, results that were attributed to transport of PFA into the sarcoplasmic Reticulum lumen and its subsequent complexation with Ca2+. Thus, results from these studies indicate the presence of a Pi transporter in the sarcoplasmic Reticulum membrane of mammalian skeletal muscle fibres that is (1) active at physiological concentrations of myoplasmic Pi and Ca2+ and (2) partially inhibited by PhPA. This Pi transporter represents a link between changes in myoplasmic [Pi] and subsequent changes in sarcoplasmic Reticulum luminal [Pi]. It might therefore play a role in the delayed metabolic impairment of sarcoplasmic Reticulum Ca2+ release seen during muscle fatigue, which should occur abruptly once the Ca--Pi solubility product is exceeded in the sarcoplasmic Reticulum lumen
