1,721,248 research outputs found

    Ryanodine receptor type 3: why another ryanodine receptor isoform?

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    The family of ryanodine receptor (RyR) genes encodes three highly related Ca2+ release channels: RyR1, RyR2 and RyR3. Until about 10 years ago, RyRs were essentially known only for being the Ca2+ release channels of the sarcoplasmic reticulum of striated muscles, because of the high levels of expression of the RyR1 and RyR2 isoforms in skeletal and cardiac muscles, respectively. In contrast with the above picture, the RyR3 gene has been found not to be preferentially expressed in one specific tissue, but rather to be widely expressed in various cells. This wide expression pattern has been subsequently observed also for the RyR1 and RyR2 genes, which in addition to their preferential expression in striated muscles, have been found expressed also in several other cell types, although at lower levels than in striated muscles. Thus a closer look reveals that in several cells of vertebrates two or even three RyR isoforms can be co-expressed. In this chapter we will review published work on the RyR3 gene and discuss a model where co-expression of different RyR channel isoforms is interpreted as an evolutionary solution to provide, by functional interactions of distinct isoforms of Ca2+ release channels, the several types of vertebrate cells with the cell-specific Ca2+ release machinery required for generating the sophisticated intracellular Ca2+ signals needed for optimal regulation of their functions

    Growth factors, growth inhibitors and cell cycle control (review)

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    Decisions about growth or quiescence are operated in the cells by a complex signal processing machinery. This machinery is built by a network of proteins that internalize these stimulatory signals from the extracellular environment across the plasmamembrane, through the cytoplasm and finally into the nucleus. Most of the information about the genes which encode the proteins that take part in this process have been obtained from studies of their aberrant alleles or oncogenes. It has become clear lately that the cell also processes negative feedback mechanisms to check this process so that it may operate error free

    Ryanodine receptors: how many, where and why?

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    Ryanodine receptors are intracellular Ca2+ channels that have been known for more than a decade to have a role in releasing Ca2+ from the sarcoplasmic reticulum to regulate contraction in skeletal and cardiac muscle fibres. Vincenzo Sorrentino and Pompeo Volpe review some recent developments: the ryanodine receptor channels have now been found to be expressed in the central nervous system, and the cloning of a third ryanodine receptor gene (RYR3) has revealed that this new isoform is widely expressed in several tissues and cells. In consequence, the view of ryanodine receptors as Ca2+ channels of muscle cells is rapidly changing, and these channels seem set to take a more central position on the stage of intracellular Ca2+ signalling

    The ryanodine receptor family of intracellular calcium release channels

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    Molecular studies have provided data on the nature and function of the intracellular calcium release channels. Two distinct classes of channels that mediate release of calcium from intracellular stores have been identified. The first is sensitive to InsP3 and is referred to as the InsP3 receptor family and the second is sensitive to a nonphysiological ligand, the plant alkaloid ryanodine (Ry), hence the name Ry receptors (RyR). These two classes of calcium release channels have general structural similarities: the active channels have a tetrameric structure in which four subunits assemble to form the functional channel. This chapter focuses only on the RyRs. Preset knowledge about the contribution of RyR to calcium signaling is extending from its original field of interest, namely, muscle physiology, to several other areas. Along with their fundamental role in regulating skeletal and cardiac muscle contraction, a functional involvement of RyRs in different central nervous system (CNS) activities, such as long-term potentiation (LTP) and long-term depression (LTD) has been proposed. Research suggests that these channels are present and functional in many other cell types, in addition to muscle and neuron cells. © 1995 Academic Press Inc

    Sarcoplasmic reticulum: structural determinants and protein dynamics

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    The sarcoplasmic reticulum is a unique organelle found in muscle cells that is dedicated to the regulation of Ca(2+) homeostasis and activation of myofilament contraction. The functional requirement for an efficient and synchronous activation of Ca(2+) release from the SR, following the depolarization of the plasma membrane, accounts for the complex three-dimensional organization of internal membranes observed in muscle cells and for the localization of proteins at specific sites of the SR. Recent advancements in understanding the molecular basis of SR structure and function have greatly increased our understanding of muscle cellular physiology and biology. Parallel work has revealed that several human diseases affecting skeletal and cardiac tissues are linked to either mutations or altered post-translational modifications of SR proteins

    Expression of the ryanodine receptor type 3 in skeletal muscle. A new partner in excitation-contraction coupling?

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    Mobilization of Ca2+ from the endoplasmic reticulum (ER) is mediated by two related groups of Ca2+ release channels, the inositol 1,4,5 trisphosphate (InsP3) receptors and the ryanodine receptors. The InsP3 receptors have been studied in a large number of cells where they regulate many different activities upon stimulation with a variety of agonists. Ryanodine receptors have been essentially studied with respect to their role in regulating muscle contraction in both cardiac and skeletal muscles. In the recent years, InsP3 receptors and ryanodine receptors have been found to be co-expressed in neurons and other cell types, including smooth muscle cells. This emerging picture reveals that within one cell different combinations of two or more isoforms of Ca2+ release channels (i.e., multiple InsP3 receptors and/or ryanodine receptors) can be expressed at the same time. New data on the expression of two isoforms of ryanodine receptors in developing skeletal muscles or in specialized adult muscles have provided initial ground to test the hypothesis that combinations of various Ca2+ release channels may be relevant to adapt the modality of Ca2+ release to regulation of specific cellular functions

    Structure and molecular organisation of the sarcoplasmic reticulum of skeletal muscle fibers

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    Activation of muscle contraction is a rapid event that is initiated by depolarization of the plasma membrane and transverse (T) tubules, which following transduction in the interior of the muscle cell, activate the release of calcium from the sarcoplasmic reticulum (SR). Pioneer studies using electron microscopy defined the organization of the sarcoplasmic reticulum and the details of the junctions between sarcoplasmic reticulum and T tubules, which are essential for translating the electrical signal on the plasma membrane to calcium release from the sarcoplasmic reticulum. Molecular biology and biochemistry studies have revealed the presence of several proteins located on the sarcoplasmic reticulum, some of which participate together with the ryanodine receptors to the assembly of a large multi-protein complex, while others, like the calcium pumps, have independent localization and activities. As a whole, the current view of this system contemplates the existence of a high level of structural organization in the sarcoplasmic reticulum with respect to the localization of ryanodine receptors and other proteins. In this review we shall summarize studies on the expression and possible functional significance of the ryanodine receptor type 3 in mammalian skeletal muscles and recent studies aimed to dissect the mechanisms that establish the organization of the SR in striated muscles
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