scholarly journals InsP3-induced Ca2+ excitability of the endoplasmic reticulum.

1995 ◽  
Vol 6 (8) ◽  
pp. 945-951 ◽  
Author(s):  
J Keizer ◽  
Y X Li ◽  
S Stojilković ◽  
J Rinzel
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Types ◽  
Smooth Muscle Contraction ◽  
Xenopus Laevis Oocytes ◽  
Ip3 Receptor ◽  
Inositol 1,4,5 Trisphosphate ◽  
Great Progress ◽  
Key Features ◽  
Experimental Findings ◽  
Made In

Oscillations in intracellular Ca2+ can be induced by a variety of cellular signalling processes (Woods et al., 1986; Berridge 1988; Jacob et al., 1988) and appear to play a role in secretion (Stojilković et al., 1994), fertilization (Miyazaki et al., 1993), and smooth muscle contraction (Iino and Tsukioka, 1994). Recently, great progress has been made in understanding the mechanisms involved in a particular class of Ca2+ oscillation, associated with the second messenger inositol 1,4,5-trisphosphate (InsP3) (Berridge, 1993). Working in concert with intracellular Ca2+, InsP3 controls Ca2+ release via the InsP3 receptor in the endoplasmic reticulum (ER) (Berridge and Irvine, 1989). The IP3 receptor is regulated by its coagonists InsP3 and Ca2+, which both activate and inhibit Ca2+ release (Finch et al., 1991; Bezprozvanny et al., 1991; De Young and Keizer, 1992). These processes, together with the periodic activation of Ca2+ uptake into the ER, have been identified as key features in the mechanism of InsP3-induced Ca2+ oscillations in pituitary gonadotrophs (Li et al., 1994), Xenopus laevis oocytes (Lechleiter and Clapham, 1992; Atri et al., 1993), and other cell types (Keizer and De Young, 1993). Earlier discussions and models of InsP3-induced Ca2+ oscillations focused on the nature and number of internal releasable pools of Ca2+ (Goldbeter et al., 1990; Swillens and Mercan, 1990; Somogyi and Stucki, 1991), the importance of oscillations in InsP3 (Meyer and Stryer, 1988), and other issues not based on detailed experimental findings in specific cells types.

Regulation of Ca2+-release-activated Ca2+ current (Icrac) by ryanodine receptors in inositol 1,4,5-trisphosphate-receptor-deficient DT40 cells

2001 ◽  
Vol 360 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Kirill KISELYOV ◽  
Dong Min SHIN ◽  
Nikolay SHCHEYNIKOV ◽  
Tomohiro KUROSAKI ◽  
Shmuel MUALLEM
Keyword(s):  
Time Course ◽  
Ryanodine Receptors ◽  
Cell Types ◽  
Ruthenium Red ◽  
General Mechanism ◽  
Inward Rectification ◽  
Wild Type ◽  
Ip3 Receptor ◽  
Inositol 1,4,5 Trisphosphate ◽  
Dt40 Cells

Persistence of capacitative Ca2+ influx in inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)-deficient DT40 cells (DT40IP3R-/−) raises the question of whether gating of Ca2+-release activated Ca2+ current (Icrac) by conformational coupling to Ca2+-release channels is a general mechanism of gating of these channels. In the present work we examined the properties and mechanism of activation of Icrac Ca2+ current in wild-type and DT40IP3R-/− cells. In both cell types passive depletion of internal Ca2+ stores by infusion of EGTA activated a Ca2+ current with similar characteristics and time course. The current was highly Ca2+-selective and showed strong inward rectification, all typical of Icrac. The activator of ryanodine receptor (RyR), cADP-ribose (cADPR), facilitated activation of Icrac, and the inhibitors of the RyRs, 8-N-cADPR, ryanodine and Ruthenium Red, all inhibited Icrac activation in DT40IP3R-/− cells, even after complete depletion of intracellular Ca2+ stores by ionomycin. Wild-type and DT40IP3R-/− cells express RyR isoforms 1 and 3. RyR levels were adapted in DT40IP3R-/− cells to a lower RyR3/RyR1 ratio than in wild-type cells. These results suggest that IP3Rs and RyRs can efficiently gate Icrac in DT40 cells and explain the persistence of Icrac gating by internal stores in the absence of IP3Rs.

Regulation of inositol 1,4,5-trisphosphate receptors

1993 ◽  
Vol 184 (1) ◽  
pp. 161-182 ◽  
Author(s):  
I. C. Marshall ◽  
C. W. Taylor
Keyword(s):  
Splice Variants ◽  
Divalent Cations ◽  
Cell Types ◽  
Smooth Muscle Contraction ◽  
Receptor Activation ◽  
Receptor Subtypes ◽  
Inositol 1,4,5 Trisphosphate ◽  
Specific Receptors ◽  
Rapid Generation ◽  
Allosteric Regulators

Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] is a soluble second messenger responsible for the generation of highly organized Ca2+ signals in a variety of cell types. These Ca2+ signals control many cellular responses, including cell growth, fertilization, smooth muscle contraction and secretion. Ins(1,4,5)P3 is produced at the plasma membrane following receptor activation, but rapidly diffuses into the cytosol, where it binds to specific receptors through which it mobilizes intracellular Ca2+ stores. The actions of Ins(1,4,5)P3 within cells are tightly controlled: enzymes control the rapid generation and metabolism of Ins(1,4,5)P3 following receptor activation; multiple Ins(1,4,5)P3 receptor subtypes and splice variants exist, some of which are differentially expressed between cell types and at different stages of development; and Ins(1,4,5)P3 receptors are the targets for a number of allosteric regulators, including protein kinases, ATP and divalent cations. Understanding how cells control the Ca(2+)-mobilizing activity of Ins(1,4,5)P3 will be important if we are to unravel the mechanisms that underlie the complex arrangements of Ca2+ signals.

Partial inhibition of SERCA is responsible for extracellular Ca2+ dependence of AlF–4-induced [Ca2+]i oscillations in rat pancreatic

2003 ◽  
Vol 285 (5) ◽  
pp. C1142-C1149 ◽  
Author(s):  
Seon Ah Chong ◽  
Soo Young Hong ◽  
Seok Jun Moon ◽  
Jee Won Park ◽  
Jeong-Hee Hong ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
G Proteins ◽  
Acinar Cells ◽  
Cell Types ◽  
Pancreatic Acinar Cells ◽  
Protein Activation ◽  
Partial Inhibition ◽  
G Protein Activation ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Ca

AlF4-is known to generate oscillations in intracellular Ca2+ concentration ([Ca2+]i) by activating G proteins in many cell types. However, in rat pancreatic acinar cells, AlF4--evoked [Ca2+]i oscillations were reported to be dependent on extracellular Ca2+, which contrasts with the [Ca2+]i oscillations induced by cholecystokinin (CCK). Therefore, we investigated the mechanisms by which AlF4- generates extracellular Ca2+-dependent [Ca2+]i oscillations in rat pancreatic acinar cells. AlF4--induced [Ca2+]i oscillations were stopped rapidly by the removal of extracellular Ca2+ and were abolished on the addition of 20 mM caffeine and 2 μM thapsigargin, indicating that Ca2+ influx plays a crucial role in maintenance of the oscillations and that an inositol 1,4,5-trisphosphate-sensitive Ca2+ store is also required. The amount of Ca2+ in the intracellular Ca2+ store was decreased as the AlF4--induced [Ca2+]i oscillations continued. Measurement of 45Ca2+ influx into isolated microsomes revealed that AlF4-directly inhibited sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). The activity of plasma membrane Ca2+-ATPase during AlF4- stimulation was not significantly different from that during CCK stimulation. After partial inhibition of SERCA with 1 nM thapsigargin, 20 pM CCK-evoked [Ca2+]i oscillations were dependent on extracellular Ca2+. This study shows that AlF4- induces [Ca2+]i oscillations, probably by inositol 1,4,5-trisphosphate production via G protein activation but that these oscillations are strongly dependent on extracellular Ca2+ as a result of the partial inhibition of SERCA.

Genetic modification of somatic cells for producing animal models and for cellular transplantation

2006 ◽  
Vol 18 (8) ◽  
pp. 811
Author(s):  
Robert B. Norgren
Keyword(s):  
Stem Cells ◽  
Animal Models ◽  
Human Disease ◽  
Adult Stem Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cellular Transplantation ◽  
Great Progress ◽  
Made In

Great progress has been made in two technologies related to biomedical research: (1) manipulating the genomes of cells; and (2) inducing stem cells in culture to differentiate into potentially useful cell types. These technologies can be used to create animal models of human disease and to provide cells for transplantation to ameliorate human disease. Both embryonic stem cells and adult stem cells have been studied for these purposes. Genetically modified somatic cells provide another source of cells for creating animal models and for cellular transplantation.

scholarly journals Differential Modulation of SERCA2 Isoforms by Calreticulin

1998 ◽  
Vol 142 (4) ◽  
pp. 963-973 ◽  
Author(s):  
Linu M. John ◽  
James D. Lechleiter ◽  
Patricia Camacho
Keyword(s):  
Endoplasmic Reticulum ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Xenopus Laevis Oocytes ◽  
Differential Modulation ◽  
Functional Differences ◽  
Selective Targeting ◽  
Inositol 1,4,5 Trisphosphate ◽  
Alternatively Spliced ◽  
Wave Properties

In Xenopus laevis oocytes, overexpression of calreticulin suppresses inositol 1,4,5-trisphosphate-induced Ca2+ oscillations in a manner consistent with inhibition of Ca2+ uptake into the endoplasmic reticulum. Here we report that the alternatively spliced isoforms of the sarcoendoplasmic reticulum Ca2+-ATPase (SERCA)2 gene display differential Ca2+ wave properties and sensitivity to modulation by calreticulin. We demonstrate by glucosidase inhibition and site-directed mutagenesis that a putative glycosylated residue (N1036) in SERCA2b is critical in determining both the selective targeting of calreticulin to SERCA2b and isoform functional differences. Calreticulin belongs to a novel class of lectin ER chaperones that modulate immature protein folding. In addition to this role, we suggest that these chaperones dynamically modulate the conformation of mature glycoproteins, thereby affecting their function.

scholarly journals IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Benjamin Bonneau ◽  
Hideaki Ando ◽  
Katsuhiro Kawaai ◽  
Matsumi Hirose ◽  
Hiromi Takahashi-Iwanaga ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Physiological State ◽  
Binding Pocket ◽  
Binding Domain ◽  
Ip3 Receptor ◽  
Antiapoptotic Protein ◽  
Inositol 1,4,5 Trisphosphate ◽  
Apoptosis Regulation

IRBIT is a molecule that interacts with the inositol 1,4,5-trisphosphate (IP3)-binding pocket of the IP3 receptor (IP3R), whereas the antiapoptotic protein, Bcl2l10, binds to another part of the IP3-binding domain. Here we show that Bcl2l10 and IRBIT interact and exert an additive inhibition of IP3R in the physiological state. Moreover, we found that these proteins associate in a complex in mitochondria-associated membranes (MAMs) and that their interplay is involved in apoptosis regulation. MAMs are a hotspot for Ca2+ transfer between endoplasmic reticulum (ER) and mitochondria, and massive Ca2+ release through IP3R in mitochondria induces cell death. We found that upon apoptotic stress, IRBIT is dephosphorylated, becoming an inhibitor of Bcl2l10. Moreover, IRBIT promotes ER mitochondria contact. Our results suggest that by inhibiting Bcl2l10 activity and promoting contact between ER and mitochondria, IRBIT facilitates massive Ca2+ transfer to mitochondria and promotes apoptosis. This work then describes IRBIT as a new regulator of cell death.

scholarly journals Calcium-dependent Clustering of Inositol 1,4,5-Trisphosphate Receptors

1998 ◽  
Vol 9 (6) ◽  
pp. 1465-1478 ◽  
Author(s):  
Bridget S. Wilson ◽  
Janet R. Pfeiffer ◽  
Alexander J. Smith ◽  
Janet M. Oliver ◽  
Jon A. Oberdorf ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Phospholipase C ◽  
Cellular Response ◽  
Immunoglobulin E ◽  
Cell Types ◽  
Resting Cells ◽  
Type Ii ◽  
Receptor Clustering ◽  
Calcium Dependent ◽  
Inositol 1,4,5 Trisphosphate

Rat basophilic leukemia (RBL-2H3) cells predominantly express the type II receptor for inositol 1,4,5-trisphosphate (InsP3), which operates as an InsP3-gated calcium channel. In these cells, cross-linking the high-affinity immunoglobulin E receptor (FcεR1) leads to activation of phospholipase C γ isoforms via tyrosine kinase- and phosphatidylinositol 3-kinase-dependent pathways, release of InsP3-sensitive intracellular Ca2+ stores, and a sustained phase of Ca2+ influx. These events are accompanied by a redistribution of type II InsP3 receptors within the endoplasmic reticulum and nuclear envelope, from a diffuse pattern with a few small aggregates in resting cells to large isolated clusters after antigen stimulation. Redistribution of type II InsP3 receptors is also seen after treatment of RBL-2H3 cells with ionomycin or thapsigargin. InsP3 receptor clustering occurs within 5–10 min of stimulus and persists for up to 1 h in the presence of antigen. Receptor clustering is independent of endoplasmic reticulum vesiculation, which occurs only at ionomycin concentrations >1 μM, and maximal clustering responses are dependent on the presence of extracellular calcium. InsP3 receptor aggregation may be a characteristic cellular response to Ca2+-mobilizing ligands, because similar results are seen after activation of phospholipase C-linked G-protein-coupled receptors; cholecystokinin causes type II receptor redistribution in rat pancreatoma AR4–2J cells, and carbachol causes type III receptor redistribution in muscarinic receptor-expressing hamster lung fibroblast E36M3R cells. Stimulation of these three cell types leads to a reduction in InsP3 receptor levels only in AR4–2J cells, indicating that receptor clustering does not correlate with receptor down-regulation. The calcium-dependent aggregation of InsP3 receptors may contribute to the previously observed changes in affinity for InsP3 in the presence of elevated Ca2+ and/or may establish discrete regions within refilled stores with varying capacity to release Ca2+ when a subsequent stimulus results in production of InsP3.

scholarly journals SERCA pump activity is physiologically regulated by presenilin and regulates amyloid β production

2008 ◽  
Vol 181 (7) ◽  
pp. 1107-1116 ◽  
Author(s):  
Kim N. Green ◽  
Angelo Demuro ◽  
Yama Akbari ◽  
Brian D. Hitt ◽  
Ian F. Smith ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Critical Role ◽  
Amyloid Β ◽  
Physiological Role ◽  
Xenopus Laevis Oocytes ◽  
Inositol 1,4,5 Trisphosphate ◽  
Pump Activity ◽  
Steady State Levels ◽  
Serca Pump ◽  
Low Levels

In addition to disrupting the regulated intramembraneous proteolysis of key substrates, mutations in the presenilins also alter calcium homeostasis, but the mechanism linking presenilins and calcium regulation is unresolved. At rest, cytosolic Ca2+ is maintained at low levels by pumping Ca2+ into stores in the endoplasmic reticulum (ER) via the sarco ER Ca2+-ATPase (SERCA) pumps. We show that SERCA activity is diminished in fibroblasts lacking both PS1 and PS2 genes, despite elevated SERCA2b steady-state levels, and we show that presenilins and SERCA physically interact. Enhancing presenilin levels in Xenopus laevis oocytes accelerates clearance of cytosolic Ca2+, whereas higher levels of SERCA2b phenocopy PS1 overexpression, accelerating Ca2+ clearance and exaggerating inositol 1,4,5-trisphosphate–mediated Ca2+ liberation. The critical role that SERCA2b plays in the pathogenesis of Alzheimer's disease is underscored by our findings that modulating SERCA activity alters amyloid β production. Our results point to a physiological role for the presenilins in Ca2+ signaling via regulation of the SERCA pump.

scholarly journals Calcium release in HSY cells conforms to a steady-state mechanism involving regulation of the inositol 1,4,5-trisphosphate receptor Ca2+ channel by luminal [Ca2+].

1996 ◽  
Vol 132 (4) ◽  
pp. 607-616 ◽  
Author(s):  
A Tanimura ◽  
R J Turner
Keyword(s):  
Steady State ◽  
Calcium Release ◽  
Cell Types ◽  
Significant Shift ◽  
Ip3 Receptor ◽  
Permeabilized Cells ◽  
Fura 2 ◽  
State Process ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

In many cell types, low concentrations of inositol 1,4,5-trisphosphate (IP3) release only a portion of the intracellular IP3-sensitive Ca2+ store, a phenomenon known as "quantal" Ca2+ release. It has been suggested that this effect is a result of reduced activity of the IP3-dependent Ca2+ channel with decreasing calcium concentration within the IP3-sensitive store ([Ca2+]s). To test this hypothesis, the properties of IP3-dependent Ca2+ release in single saponin-permeabilized HSY cells were studied by monitoring [Ca2+]s using the Ca(2+)-sensitive fluorescent dye mag-fura-2. In permeabilized cells, blockade of the sarco/ER Ca(2+)-ATPase pump in stores partially depleted by IP3 induced further Ca2+ release via an IP3-dependent route, indicating that Ca2+ entry via the sarco/ER Ca(2+)-ATPase pump had been balanced by Ca2+ loss via the IP3-sensitive channel before pump inhibition. IP3-dependent Mn2+ entry, monitored via quenching of luminal mag-fura-2 fluorescence, was readily apparent in filled stores but undetectable in Ca(2+)-depleted stores, indicating markedly reduced IP3-sensitive channel activity in the latter. Also consistent with reduced responsiveness of Ca(2+)-depleted stores to IP3, the initial rate of refilling of these stores was unaffected by the presence of 0.3 microM IP3, a concentration that was clearly effective in eliciting Ca2+ release from filled stores. Analysis of the rate of Ca2+ release at various IP3 concentrations indicated a significant shift of the IP3 dose response toward higher [IP3] with decreasing [Ca2+]s. We conclude that IP3-dependent Ca2+ release in HSY cells is a steady-state process wherein Ca2+ efflux via the IP3 receptor Ca2+ channel is regulated by [Ca2+]s, apparently via changes in the sensitivity of the channel to IP3.

Prevalence of the pit and antipit in the genus Glycine

1987 ◽  
Vol 45 ◽  
pp. 986-987
Author(s):  
R. W. Yaklich ◽  
E. L. Vigil ◽  
W. P. Wergin
Keyword(s):  
Amino Acids ◽  
Endoplasmic Reticulum ◽  
Glycine Max ◽  
Seed Coat ◽  
Cell Types ◽  
Abaxial Surface ◽  
Legume Seed ◽  
Initial Report ◽  
Cone Cells ◽  
Glycine Max L

The legume seed coat is the site of sucrose unloading and the metabolism of imported ureides and synthesis of amino acids for the developing embryo. The cell types directly responsible for these functions in the seed coat are not known. We recently described a convex layer of tissue on the inside surface of the soybean (Glycine max L. Merr.) seed coat that was termed “antipit” because it was in direct opposition to the concave pit on the abaxial surface of the cotyledon. Cone cells of the antipit contained numerous hypertrophied Golgi apparatus and laminated rough endoplasmic reticulum common to actively secreting cells. The initial report by Dzikowski (1936) described the morphology of the pit and antipit in G. max and found these structures in only 68 of the 169 seed accessions examined.

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