Endoplasmic reticulum, calcium

Sigma-2 receptors may represent components of a novel apoptotic pathway which could play a role in regulation of cell proliferation or in development. This pathway consists of intracellular membrane bound sigma-2 receptors, loeal-ized on organelles known to store calcium (endoplasmic reticulum and mitochondria) and with the ability to cause release of calcium from these stores. Calcium signals may be utilized in normal eell signalling and/or for the induction of apoptosis. Elucidation of the apoptotic pathway will require delineation of the structure of sigma-2 receptors and other downstream proteins with which the receptor may interact. 

Mammals synthesize phosphatidylserine (PS) in a calcium ion-dependent reaction involving aminoalcohol exchange (Figure 25.21). The enzyme catalyzing this reaction is associated with the endoplasmic reticulum and will accept phosphatidylethanolamine (PE) and other phospholipid substrates. A mitochondrial PS decarboxylase can subsequently convert PS to PE. No other pathway converting serine to ethanolamine has been found. 

Calcium channels in the plasma membrane activated after receptor-mediated calcium release from intracellular stores. Diese channels are present in many cellular types and play pivotal roles in a multitude of cell functions. It was recently shown that Orai proteins are the pore-forming subunit of CRAC channels. They are activated by STIM proteins that sense the Ca2+ content of the endoplasmic reticulum. 

In the sarcoplasm of smooth muscle cells there is a membrane bound compartment usually referred to as the SR by analogy with skeletal muscle. However, it is not at all clear that the interior of these membrane-bound regions are continuous as they are in skeletal muscle. The primary properties of this system seem to be quite similar to those of the endoplasmic reticulum of many other cell types. In general, calcium is concentrated into the membrane-bound reticulum and then released to initiate the characteristic action of the cell. 

Figure 2. Reporting of cytosolic free calcium levels by indo-1. Increases in cytosolic calcium, due either to entry of extracellular calcium via calcium channels or to release of intracellular calcium sequestered in organelles such as smooth endoplasmic reticulum, results in formation of the indo-l-calcium complex. Fluorescence intensity at 400 nm (excitation at 340 nm) is proportional to the concentration of this complex the dissociation constant for this complex is about 250 nff (24), making this probe useful for detecting calcium activities in the range of 25 to 2500 nJ. ...

Figure 3. Reporting of intracellular calcium sequestration by chlorotetracycline (CTC). CTC preferentially partitions into cell membranes and its fluorescence in this environment is sensitive to calcium bound to the membrane therefore its signal (excitation AOO nm, emission 530 nm) will come largely from organelles that bind or sequester calcium, such as smooth endoplasmic reticulum or mitochondria. Release of calcium from such organelles is accompanied by dissociation of the calcium-CTC complex, a decrease in CTC fluorescence and efflux of unbound probe from the organelle and from the cell.

There is evidence for immunosuppressive effects of PAHs in rodents (Davila et al. 1997). For example, strong immunosuppressive effects were reported in mice that had been dosed with benzo[fl]pyrene and 3-methyl cholanthrene, effects that persisted for up to 18 months (Environmental Health Criteria 202). Multiple immu-notoxic effects have been reported in rodents, and there is evidence that these result from disturbance of calcium homeostasis (Davila et al. 1997). PAHs can activate protein tyrosine kinases in T cells that initiate the activation of a form of phospholipase C. Consequently, release of inositol triphosphate—a molecule that immobilizes Ca + from storage pools in the endoplasmic reticulum—is enhanced. 

Another popular assay for GPCR activation is to measure the increase in intracellular Ca2+ that occurs upon activation. GPCRs on the cell surface produce inositol triphosphate (IP3) via the action of Phospholipase C (PLC). IP3 stimulates calcium channels called IP3 receptors on the endoplasmic reticulum, which raise... 

Fragments of the endoplasmic reticulum and the golgi apparatus produce enzymes and store calcium. 

DMP also has been used to study the interaction between the endoplasmic reticulum and microtubules (Ogawa-Goto et al., 2007), the conformational changes in the outer arm dynein of Chlamydomonas in response to calcium (Sakato et al., 2007), and the secretion of the adipocyte-specific secretory protein adiponectin (Wang et al., 2007). 

Calcium is pumped out of the cytosol by Ca2+ pumps in the plasma membrane, endoplasmic reticulum, or mitochondria. 

Calumin Membrane-spanning calcium-binding protein involved in Ca2+-handling and signaling in the endoplasmic reticulum (368)... 

The smooth endoplasmic reticulum calcium pumps (SERCA) found in brain were first identified in sarcoplasmic reticulum. The three isoforms of SERCA are products of separate genes SERCA-1 is expressed in fast-twitch skeletal muscle SERCA-2a in cardiac/slow-twitch muscle SERCA-2b, an alternatively spliced form, is expressed in smooth muscle and non-muscle tissues SERCA-3 is... 

FIGURE 22-2 ATP-dependent uptake of calcium into endoplasmic reticulum and mitochondria as a function of extraorganellar Ca2+ concentration. As [Ca2+] j was raised, ATP-dependent Ca2+ uptake into the endoplasmic reticulum (ER) and mitochondria] pools increased. Data for ER uptake were determined as the amount of Ca2+ [45Ca2+] taken up by saponin-permeabilized hepatocytes after addition of ATP and in the presence of mitochondrial inhibitors. The curve for mitochondria] uptake was obtained by subtracting the ATP-dependent uptake in the presence of these inhibitors from that in the absence of inhibitors. For additional details consult Burgess et al. [31]. Stylized data taken from results originally reported in Burgess etal. [31]. (Redrawn and modified from reference [4] with permission of Landes Bioscience.)... 

Rossier, M. F. and Putney, J. W. Jr. The identity of the calcium storing inositol 1,4,5-trisphosphate-sensitive organelle in non-muscle cells Calciosome, endoplasmic reticulum... or both Trends Neurosci. 14 30-314,1991. 

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