Expression and functional characterization of SCaMPER: a sphingolipid-modulated calcium channel of cardiomyocytes

2003 ◽  
Vol 284 (3) ◽  
pp. C780-C790 ◽  
Author(s):  
Amy L. Cavalli ◽  
Nicole W. O'Brien ◽  
Steven B. Barlow ◽  
Romeo Betto ◽  
Christopher C. Glembotski ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Calcium Release ◽  
Cardiac Tissue ◽  
Ryanodine Receptors ◽  
Functional Characterization ◽  
Substantial Reduction ◽  
Pcr Cloning ◽  
Cellular Events ◽  
T Tubules ◽  
And Function

Calcium channels are important in a variety of cellular events including muscle contraction, signaling, proliferation, and apoptosis. Sphingolipids have been recognized as mediators of intracellular calcium release through their actions on a calcium channel, sphingolipid calcium release-mediating protein of the endoplasmic reticulum (SCaMPER). The current study investigates the expression and function of SCaMPER in cardiomyocytes. Northern analyses and RT-PCR cloning and sequencing revealed SCaMPER expression in both human and rat cardiac tissue. Immunofluorescence and Western blot analyses demonstrated that SCaMPER is abundant in cardiac tissue and is localized to the sarcotubular junction. This was confirmed by the colocalization of SCaMPER with dihydropyridine and ryanodine receptors by confocal microscopy. Purified T tubules were shown to contain SCaMPER and immunoelectron micrographs suggested that SCaMPER is located to the junctional T tubules, but a junctional SR localization cannot be ruled out. The sphingolipid ligand for SCaMPER, sphingosylphosphorylcholine (SPC), initiated calcium release from the cardiomyocyte SR. Importantly, antisense knockdown of SCaMPER mRNA produced a substantial reduction of sphingolipid-induced calcium release, suggesting that SCaMPER is a potentially important calcium channel of cardiomyocytes.

Modulation of type-1 Ins(1,4,5)P3 receptor channels by the FK506-binding protein, FKBP12

2002 ◽  
Vol 361 (2) ◽  
pp. 401-407 ◽  
Author(s):  
Sheila L. DARGAN ◽  
Edward J. A. LEA ◽  
Alan P. DAWSON
Keyword(s):  
Lipid Bilayers ◽  
Calcium Release ◽  
Single Channel ◽  
Binding Protein ◽  
Ryanodine Receptors ◽  
Fk506 Binding Protein ◽  
Single Channel Activity ◽  
And Function ◽  
First Time

FK506-binding protein (FKBP12) is highly expressed in neuronal tissue, where it is proposed to localize calcineurin to intracellular calcium-release channels, ryanodine receptors and Ins(1,4,5)P3 receptors (InsP3Rs). The effects of FKBP12 on ryanodine receptors have been well characterized but the nature and function of binding of FKBP12 to InsP3R is more controversial, with evidence for and against a tight interaction between these two proteins. To investigate this, we incorporated purified type-1 InsP3R from rat cerebellum into planar lipid bilayers to monitor the effects of exogenous recombinant FKBP12 on single-channel activity, using K+ as the current carrier. Here we report for the first time that FKBP12 causes a substantial change in single-channel properties of the type-1 InsP3R, specifically to increase the amount of time the channel spends in a fully open state. In the presence of ATP, FKBP12 can also induce co-ordinated gating with neighbouring receptors. The effects of FKBP12 were reversed by FK506. We also present data showing that rapamycin, at sub-optimal concentrations of Ins(2,4,5)P3, decreases the rate of calcium release from cerebellar microsomes. These results provide evidence for a direct functional interaction between FKBP12 and the type-1 InsP3R.

scholarly journals Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

2010 ◽  
Vol 2 (11) ◽  
pp. a003996-a003996 ◽  
Author(s):  
J. T. Lanner ◽  
D. K. Georgiou ◽  
A. D. Joshi ◽  
S. L. Hamilton
Keyword(s):  
Calcium Release ◽  
Ryanodine Receptors ◽  
And Function

scholarly journals Calcium Release Channels: Structure and Function of IP3 Receptors and Ryanodine Receptors

2021 ◽  
Author(s):  
Kellie A Woll ◽  
Filip Van Petegem
Keyword(s):  
Small Molecules ◽  
Calcium Release ◽  
Current Knowledge ◽  
Ryanodine Receptors ◽  
Ip3 Receptors ◽  
Electron Microscopic ◽  
Channel Opening ◽  
And Function ◽  
Opening And Closing ◽  
Common Architecture

Ca2+-release channels are giant membrane proteins that control the release of Ca2+ from the endoplasmic and sarcoplasmic reticulum. The two members, ryanodine receptors (RyRs) and inositol-1,4,5-trisphosphate Receptors (IP3Rs), are evolutionarily related and are both activated by cytosolic Ca2+. They share a common architecture, but RyRs have evolved additional modules in the cytosolic region. Their massive size allows for the regulation by tens of proteins and small molecules, which can affect the opening and closing of the channels. In addition to Ca2+, other major triggers include IP3 for the IP3Rs, and depolarization of the plasma membrane for a particular RyR subtype. Their size has made them popular targets for study via electron microscopic methods, with current structures culminating near 3Å. The available structures have provided many new mechanistic insights int the binding of auxiliary proteins and small molecules, how these can regulate channel opening, and the mechanisms of disease-associated mutations. They also help scrutinize previously proposed binding sites, as some of these are now incompatible with the structures. Many questions remain around the structural effects of post-translational modifications, additional binding partners, and the higher-order complexes these channels can make in situ. This review summarizes our current knowledge about the structures of Ca2+-release channels and how this informs on their function.

Structure and function of the neuronal endomembrane system

1993 ◽  
Vol 51 ◽  
pp. 98-99
Author(s):  
Maryann E. Martone ◽  
Victoria M. Simpliciano ◽  
Ying Zhang ◽  
Thomas J. Deerinck ◽  
Mark H. Ellisman
Keyword(s):  
Intracellular Calcium ◽  
Calcium Release ◽  
Smooth Endoplasmic Reticulum ◽  
Ryanodine Receptors ◽  
Cell Types ◽  
Calcium Stores ◽  
Endomembrane System ◽  
Ip3 Receptor ◽  
And Function ◽  
Cerebellar Purkinje Neurons

Components of the endomembrane system in a variety of cell types appear to function in the storage and release of calcium similar to the muscle sarcoplasmic reticulum. Many proteins involved in intracellular calcium regulation in skeletal or smooth muscle, e.g. Ca++ ATPase, calsequestrin, the inositol l,4,5,trisphosphate (TP3) receptor and the ryanodine binding protein, are found in the nervous system where they are particularly abundant within the smooth endoplasmic reticulum (SER) of cerebellar Purkinje neurons. Immunolocalization studies suggest, however, that calcium regulatory proteins are not uniformly distributed within the SER but are concentrated in or excluded from certain domains. For example, the IP3 and ryanodine receptors, two distinct calcium channels which mediate calcium release by different ligands, are found associated with the SER in cell bodies and dendrites of chick cerebellum but only the IP3 receptor is found within dendritic spines. These results are consistent with evidence that cells may possess multiple intracellular calcium stores that are pharmacologically, spatially and perhaps physically distinct.

scholarly journals The network of calcium regulation in muscle.

2003 ◽  
Vol 50 (1) ◽  
pp. 1-30 ◽  
Author(s):  
Anthony N Martonosi ◽  
Slawomir Pikula
Keyword(s):  
Plasma Membranes ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Transport Systems ◽  
Molecular Characteristics ◽  
Plasmic Reticulum ◽  
Coordinated Expression ◽  
History Of ◽  
Cardiac Muscles ◽  
And Function

In this review the molecular characteristics and reaction mechanisms of different Ca(2+) transport systems associated with various membranes in muscle cells will be summarized. The following topics will be discussed in detail: a brief history of early observations concerning maintenance and regulation of cellular Ca(2+) homeostasis, characterization of the Ca(2+) pumps residing in plasma membranes and sarco(endo)plasmic reticulum, mitochondrial Ca(2+) transport, Ca(2+)-binding proteins, coordinated expression of Ca(2+) transport systems, a general background of muscle excitation-contraction coupling with emphasis to the calcium release channels of plasma membrane and sarcoplasmic reticulum, the structure and function of dihydropyridine and ryanodine receptors of skeletal and cardiac muscles, and finally their disposition in various types of muscles.

How Many Ryanodine Binding Sites Are Involved in Caffeine Induced Calcium Release from Sarcoplasmic Reticulum Terminal Cysternae Vesicles?

1992 ◽  
Vol 47 (1-2) ◽  
pp. 136-147 ◽  
Author(s):  
Wilhelm Hasselbach ◽  
Andrea Migala
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Channel ◽  
Binding Sites ◽  
Calcium Release ◽  
Initial Rate ◽  
Ryanodine Receptors ◽  
Stoichiometric Composition ◽  
Calcium Release Channels ◽  
Equilibrium Binding ◽  
Reported Data

Abstract The inhibition by ryanodine of caffeine induced calcium release from actively loaded heavy sarcoplasmic vesicles has been studied in order to analyse the relation between the occupancy of the vesicular calcium release channels by ryanodine and channel function. Ryanodine binding was monitored with [3H]ryanodine under ionic conditions favouring the establishment of binding equilibrium. Binding follows 1 : 1 stoichiometry yielding dissociations constants between 7 - 12 nᴍ and 12-15 pmol ryanodine/mg vesicular protein as maximum number of ryanodine binding sites. When ryanodine labeling was monitored by measuring the decline of the amplitude of caffeine induced calcium release 50% inhibition occurred at a free ryanodine concentration of 1 nM. At this concentration less than 10% of the available ryanodine binding sites are occupied. Caffeine induced calcium release is completely abolished when 3 pmol ryanodine/mg have reacted. A corresponding divergence between ryanodine binding and its effect on caffeine induced calcium release was observed when the initial rate of ryanodine binding was measured either by labeling the vesicles with [3H]ryanodine or by following the decline with time of caffeine induced calcium release. Caffein induced calcium release declines four times faster than the fraction of unoccupied ryanodine binding sites, k = 4.3 x 104 ᴍ-1 s-1 versus 1.2 x 104 ᴍ-1 s-1. The observed interrelation between the occupation of ryanodine binding sites and its effect on caffeine induced calcium release indicates that the caffeine sensitive calcium channel functions as an assembly of at least 4 ryanodine binding sites whereby the occupation of one site suffices to abolish calcium release. The stoichiometric composition appears to be not fixed but might change according to the size of the fraction of ryanodine receptors exhibiting caffeine sensitivity. The reported data were evaluated according to the algorithm derived by H. Asai and M. F. Morales, J. Biol. Chem. 4, 830-838 (1965) for the activity of a macromolecule and the extent of an inhibiting reaction.

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

Evaluation of left atrial size and function – from M-mode to 3D speckle-tracking echocardiography

2014 ◽  
Vol 155 (41) ◽  
pp. 1624-1631 ◽  
Author(s):  
Attila Nemes ◽  
Tamás Forster
Keyword(s):  
Left Atrium ◽  
Left Atrial ◽  
Functional Characterization ◽  
Left Atrial Size ◽  
Dynamic Motion ◽  
Heart Chamber ◽  
Atrial Size ◽  
Exact Measurement ◽  
Heart Cycle ◽  
And Function

Left atrium is not a passive heart chamber, because it has a dynamic motion respecting heart cycle and, in accordance with its stretching, it releases atrial natriuretic peptides. Since in the course of certain invasive procedures the size of left atrium may change substantially, its exact measurement and functional characterization are essential. The aim of the present review is to summarize echocardiographic methods for the assessment of left atrial size and functional parameters. Orv. Hetil., 2014. 155(41), 1624–1631.

Establishing a model to demonstrate physical and mathematical properties of chromatin fibres in fission yeast cells - Research in the Molecular Biophysics Lab at Hiroshima University

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 89-91
Author(s):  
Shin-ichi Tate
Keyword(s):  
Molecular Biology ◽  
Yeast Cells ◽  
Molecular Architecture ◽  
Ministry Of Education ◽  
Cellular Functions ◽  
Sports Science ◽  
Cellular Events ◽  
And Function ◽  
Education Culture ◽  
Open The Doors

The field of molecular biology has provided great insights into the structure and function of key molecules. Thanks to this area of research, we can now grasp the biological details of DNA and have characterised an enormous number of molecules in massive data bases. These 'biological periodic tables' have allowed scientists to connect molecules to particular cellular events, furthering scientific understanding of biological processes. However, molecular biology has yet to answer questions regarding 'higher-order' molecular architecture, such as that of chromatin. Chromatin is the molecular material that serves as the building block for chromosomes, the structures that carry an organism's genetic information inside of the cell's nucleus. Understanding the physical properties of chromatin is crucial in developing a more thorough picture of how chromatin's structure relate to its key cellular functions. Moreover, by establishing a physical model of chromatin, scientists will be able to open the doors into the true inner workings of the cell nucleus. Professor Shin-ichi Tate and his team of researchers at Hiroshima University's Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), are attempting to do just that. Through a five-year grant funded by the Platform for Dynamic Approaches to Living Systems from the Ministry of Education, Culture, Sports, Science and Technology, Tate is aiming to gain a clearer understanding of the structure and dynamics of chromatin.

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