scholarly journals Rapid kinetics of lipid second messengers controlled by a cGMP signalling network coordinates apical complex functions in Toxoplasma tachyzoites

2020 ◽  
Author(s):  
Nicholas J. Katris ◽  
Yoshiki Yamaryo-Botte ◽  
Jan Janouškovec ◽  
Serena Shunmugam ◽  
Christophe-Sebastien Arnold ◽  
...  
Keyword(s):  
Second Messengers ◽  
Calcium Signalling ◽  
Phospholipid Metabolism ◽  
Lipid Signalling ◽  
Cgmp Signalling ◽  
Lipid Signal ◽  
Signalling Network ◽  
Complex Functions ◽  
Rapid Kinetics ◽  
Phosphatidylinositol Phosphates

ABSTRACTHost cell invasion and subsequent egress by Toxoplasma parasites is regulated by a network of cGMP, cAMP, and calcium signalling proteins. Such eukaryotic signalling networks typically involve lipid second messengers including phosphatidylinositol phosphates (PIPs), diacylglycerol (DAG) and phosphatidic acid (PA). However, the lipid signalling network in Toxoplasma is poorly defined. Here we present lipidomic analysis of a mutant of central flippase/guanylate cyclase TgGC in Toxoplasma, which we show has disrupted turnover of signalling lipids impacting phospholipid metabolism and membrane stability. The turnover of signalling lipids is extremely rapid in extracellular parasites and we track changes in PA and DAG to within 5 seconds, which are variably defective upon disruption of TgGC and other signalling proteins. We then identify the position of each protein in the signal chain relative to the central cGMP signalling protein TgGC and map the lipid signal network coordinating conoid extrusion and microneme secretion for egress and invasion.

scholarly journals The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development

2021 ◽  
Author(s):  
Soumyaparna Das ◽  
Yiyi Chen ◽  
Jie Yan ◽  
Gustav Christensen ◽  
Soumaya Belhadj ◽  
...  
Keyword(s):  
Cell Death ◽  
Photoreceptor Cell ◽  
Second Messengers ◽  
Calcium Signalling ◽  
Clinical Applications ◽  
Photoreceptor Degeneration ◽  
Therapeutic Approaches ◽  
Cgmp Signalling ◽  
Key Aspects

AbstractThe second messengers, cGMP and Ca2+, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor cell death. This problem is exacerbated by the close connections and crosstalk between cGMP-signalling and calcium (Ca2+)-signalling in photoreceptors. In this review, we summarize key aspects of cGMP-signalling and Ca2+-signalling relevant for hereditary photoreceptor degeneration. The topics covered include cGMP-signalling targets, the role of Ca2+ permeable channels, relation to energy metabolism, calpain-type proteases, and how the related metabolic processes may trigger and execute photoreceptor cell death. A focus is then put on cGMP-dependent mechanisms and how exceedingly high photoreceptor cGMP levels set in motion cascades of Ca2+-dependent and independent processes that eventually bring about photoreceptor cell death. Finally, an outlook is given into mutation-independent therapeutic approaches that exploit specific features of cGMP-signalling. Such approaches might be combined with suitable drug delivery systems for translation into clinical applications.

Rapid kinetics of second messenger production in bitter taste

1996 ◽  
Vol 270 (3) ◽  
pp. C926-C931 ◽  
Author(s):  
A. I. Spielman ◽  
H. Nagai ◽  
G. Sunavala ◽  
M. Dasso ◽  
H. Breer ◽  
...  
Keyword(s):  
Bitter Taste ◽  
Second Messengers ◽  
Second Messenger ◽  
Mouse Strains ◽  
Protective Mechanism ◽  
Transient Nature ◽  
Sucrose Octaacetate ◽  
Rapid Kinetics ◽  
First Time

The tasting of bitter compounds may have evolved as a protective mechanism against ingestion of potentially harmful substances. We have identified second messengers involved in bitter taste and show here for the first time that they are rapid and transient. Using a quench-flow system, we have studied bitter taste signal transduction in a pair of mouse strains that differ in their ability to taste the bitter stimulus sucrose octaacetate (SOA); however, both strains taste the bitter agent denatonium. In both strains of mice, denatonium (10 mM) induced a transient and rapid increase in levels of the second messenger inositol 1,4,5-trisphosphate (IP3) with a maximal production near 75-100 ms after stimulation. In contrast, SOA (100 microM) brought about a similar increase in IP3 only in SOA-taster mice. The response to SOA was potentiated in the presence of GTP (1 microM). The GTP-enhanced SOA-response supports a G protein-mediated response for this bitter compound. The rapid kinetics, transient nature, and specificity of the bitter taste stimulus-induced IP3 formation are consistent with the role of IP3 as a second messenger in the chemoelectrical transduction of bitter taste.

scholarly journals Intercellular calcium signalling between chondrocytes and synovial cells in co-culture

1998 ◽  
Vol 329 (3) ◽  
pp. 681-687 ◽  
Author(s):  
Paola D'ANDREA ◽  
Alessandra CALABRESE ◽  
Micaela GRANDOLFO
Keyword(s):  
Gap Junctions ◽  
Intercellular Communication ◽  
Structural Changes ◽  
Articular Chondrocytes ◽  
Cell Metabolism ◽  
Second Messengers ◽  
Calcium Signalling ◽  
Cell Types ◽  
Synovial Cells ◽  
Cell Coupling

Intercellular communication allows the co-ordination of cell metabolism between tissues as well as sensitivity to extracellular stimuli. Paracrine stimulation and cell-to-cell coupling through gap junctions induce the formation of complex cellular networks that favour the intercellular exchange of nutrients and second messengers. Heterologous intercellular communication was studied in co-cultures of articular chondrocytes and HIG-82 synovial cells by measuring mechanically induced cytosolic changes in Ca2+ ion levels by digital fluorescence video imaging. In confluent co-cultures, mechanical stimulation induced intercellular Ca2+ waves that propagated to both cell types with similar kinetics. Intercellular wave spreading was inhibited by 18α-glycyrrhetinic acid and by treatments inhibiting the activation of purinoreceptors, suggesting that intercellular signalling between these two cell types occurs both through gap junctions and ATP-mediated paracrine stimulation. In rheumatoid arthritis the formation of the synovial pannus induces structural changes at the chondrosynovial junction, where chondrocyte and synovial cells come into close apposition: these results provide the first evidence for direct intercellular communication between these two cell types.

Role of phosphatidylinositide metabolism in ras-induced Xenopus oocyte maturation

1990 ◽  
Vol 10 (3) ◽  
pp. 923-929
Author(s):  
B T Pan ◽  
G M Cooper
Keyword(s):  
Xenopus Oocytes ◽  
Second Messengers ◽  
Phospholipid Metabolism ◽  
Meiotic Maturation ◽  
Ras Oncogene ◽  
Ras Protein ◽  
32P Incorporation ◽  
Kinetics Of ◽  
Oncogene Protein

Microinjection of Xenopus oocytes with ras protein (p21) was used to investigate the role of phospholipid metabolism in ras-induced meiotic maturation. Induction of meiosis by ras was compared with induction by progesterone, insulin, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Neomycin, which specifically binds to phosphatidylinositides and inhibits their metabolism, blocked meiotic maturation induced by ras or insulin but not by progesterone or TPA. In addition, p21 and TPA, but not insulin or progesterone, stimulated the incorporation of 32Pi into oocyte lipids. ras protein specifically stimulated 32P incorporation into phosphatidylinositides, whereas both ras and TPA stimulated 32P incorporation into phosphatidylcholine and phosphatidylethanolamine. The stimulatory effect of p21 on phosphatidylinositide metabolism correlated with the dose response and kinetics of ras-induced meiotic maturation. In addition, the ras oncogene protein was more potent than the proto-oncogene protein both in inducing meiotic maturation and in stimulating phosphatidylinositide metabolism. These results indicate that phosphatidylinositide turnover is required for ras-induced meiosis and suggest that phosphatidylinositide-derived second messengers mediate the biological activity of ras in Xenopus oocytes.

Lifespan regulation of conventional protein kinase C isotypes

2007 ◽  
Vol 35 (5) ◽  
pp. 1043-1045 ◽  
Author(s):  
D. Carmena ◽  
A. Sardini
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Second Messengers ◽  
Therapeutic Strategies ◽  
Kinase C ◽  
Signalling Network ◽  
Pkc Protein Kinase C ◽  
Lifespan Regulation

Plasma membrane translocation, following allosteric binding of second messengers, initiates the signal transduction process mediated by cPKC [conventional PKC (protein kinase C)] isotypes. Mechanisms regulating the lifespan of the active enzyme such as its phosphorylation, internalization, dephosphorylation and degradation are key elements of the signalling network. The understanding of such mechanisms is essential for the design of therapeutic strategies targeting PKC isoenzymes.

The Croonian Lecture, 1988 - Inositol lipids and calcium signalling

1988 ◽  
Vol 234 (1277) ◽  
pp. 359-378 ◽  
Keyword(s):  
Endoplasmic Reticulum ◽  
Calcium Release ◽  
Second Messengers ◽  
Calcium Signalling ◽  
Calcium Oscillations ◽  
Interesting Possibility ◽  
Oscillatory Mechanism ◽  
A Cell ◽  
External Stimuli ◽  
External Calcium

The response of cells to many external stimuli requires a decoding process at the membrane to transduce information into intracellular messengers. A major decoding mechanism employed by a variety of hormones, neuro­transmitters and growth factors depends on the hydrolysis of a unique inositol lipid to generate two key second messengers, diacylglycerol and inositol 1, 4, 5-trisphosphate (Ins(1, 4, 5) P 3 ). Here I examine the second messenger function of Ins(l, 4, 5) P 3 in controlling the mobilization of cal­cium. We know most about how this messenger releases calcium from internal reservoirs but less is known concerning the entry of external calcium. One interesting possibility is that Ins(1, 4, 5) P 3 might function in conjunction with its metabolic product Ins(1, 3, 4, 5) P 4 to control calcium entry through a mechanism employing a region of the endoplasmic re­ticulum as a halfway house during the transfer of calcium from outside the cell into the cytoplasm. The endoplasmic reticulum interposed be­tween the plasma membrane and the cytosol may function as a capacitor to insure against the cell being flooded with external calcium. When stimulated, cells often display remarkably uniform oscillations in intracellular calcium. At least two oscillatory patterns have been recognized suggesting the existence of separate mechanisms both of which may depend upon Ins(1, 4, 5) P 3 . In one mechanism, oscillations may be driven by periodic pulses of Ins(1, 4, 5) P 3 produced by receptors under negative feedback control of protein kinase C. The other oscillatory mechanism may depend upon Ins(1, 4, 5) P 3 unmasking a process of cal­cium-induced calcium release from the endoplasmic reticulum. The func­tion of these calcium oscillations is still unknown. This Ins(1, 4, 5) P 3 /calcium signalling system is put to many uses during the life history of a cell. It first occurs in immature oocytes, it functions during fertilization and there is an intriguing possibility that it might play a role in pattern formation during early development. Fully dif­ferentiated cells continue to employ this highly versatile system for regulating a host of functions including contraction, secretion and metabolism.

scholarly journals Modulation of cytosolic-[Ca2+] oscillations in hepatocytes results from cross-talk among second messengers. The synergism between the α1-adrenergic response, glucagon and cyclic AMP, and their antagonism by insulin and diacylglycerol manifest themselves in the control of the cytosolic-[Ca2+] oscillations

1992 ◽  
Vol 286 (3) ◽  
pp. 869-877 ◽  
Author(s):  
R Somogyi ◽  
M Zhao ◽  
J W Stucki
Keyword(s):  
Cyclic Amp ◽  
Insulin Signalling ◽  
Second Messengers ◽  
Second Messenger ◽  
Rat Hepatocytes ◽  
Oscillatory System ◽  
The Core ◽  
Oscillatory Pattern ◽  
Signalling Network ◽  
Second Messenger Pathways

Hepatocytes respond to stimulation by glycogenolytic agonists acting via phosphoinositide (PI) breakdown through oscillations of the free cytosolic concentration of Ca2+ ([Ca2+]cyt.). Since the second-messenger repertoire of hepatocytes includes many other factors besides Ca2+, we investigated to what degree the regulation of [Ca2+]cyt. oscillations is integrated into these other signalling systems. [Ca2+]cyt. was recorded in single rat hepatocytes by using the Ca(2+)-indicator fura-2. Parallel stimulation with phenylephrine (an alpha 1-adrenergic agonist of PI breakdown) and glucagon resulted in a synergistic stimulation of [Ca2+]cyt. oscillations. Direct activation of the cyclic-AMP-dependent pathway with several stimuli (forskolin, 8-bromo cyclic AMP, 8-CPT cyclic AMP) mimicked the response to glucagon. In contrast, [Ca2+]cyt. oscillations induced by various combinations of these agonists could be antagonized by the glycogenic hormone insulin. As one of the options in the insulin-signalling network, we tested a diacylglycerol activator of protein kinase C, DiC8. It also acted as an inhibitor of [Ca2+]cyt. oscillations. We investigated how these observations could be reconciled with our previously introduced model of [Ca2+]cyt. oscillations in hepatocytes [Somogyi and Stucki (1991) J. Biol. Chem. 266, 11068-11077]. First of all, the effect of calmodulin inhibitors (calmidazolium and CGS 9343 B), acting at the core of our model on the feedback of Ca2+ on Ins(1,4,5)P3-induced Ca2+ release, was not altered by the new modulators. In addition, all agonists and antagonists could be used interchangeably in combination and introduced no significant change in the oscillatory pattern or spike shape. Since the response was solely limited to frequency modulation, over- or understimulation of the oscillatory system, there is no need to create a new oscillator or to introduce further reaction steps into the core of the model. We conclude that the regulation of [Ca2+]cyt. via the explored second-messenger pathways can be embedded into the oscillatory system as modulation of rate constants already present in this model.

scholarly journals Author Correction: A calcium signalling network activates vacuolar K+ remobilization to enable plant adaptation to low-K environments

Nature Plants ◽  
2020 ◽  
Vol 6 (6) ◽  
pp. 718-718
Author(s):  
Ren-Jie Tang ◽  
Fu-Geng Zhao ◽  
Yang Yang ◽  
Chao Wang ◽  
Kunlun Li ◽  
...  
Keyword(s):  
Calcium Signalling ◽  
Plant Adaptation ◽  
Signalling Network ◽  
Low K

Regulation of calcium signalling by adenine-based second messengers

2007 ◽  
Vol 35 (1) ◽  
pp. 109-114 ◽  
Author(s):  
R. Fliegert ◽  
A. Gasser ◽  
A.H. Guse
Keyword(s):  
Transient Receptor Potential ◽  
Second Messengers ◽  
Calcium Signalling ◽  
Receptor Potential ◽  
Cell Types ◽  
Cellular Systems ◽  
Membrane Receptors ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Plasma Membrane Receptors

cADPR [cyclic ADPR (ADP-ribose)], NAADP (nicotinic acid–adenine dinucleotide phosphate) and ADPR belong to the family of adenine-containing second messengers. They are metabolically related and are all involved in the regulation of cellular Ca2+ homoeostasis. Activation of specific plasma membrane receptors is connected to cADPR formation in many cell types and tissues. In contrast receptor-mediated formation of NAADP and ADPR has been shown only in a few selected cellular systems. The intracellular Ca2+ channel triggered by cADPR is the RyR (ryanodine receptor); in the case of NAADP, both activation of RyR and a novel Ca2+ channel have been proposed. In contrast, ADPR opens the non-specific cation channel TRPM2 [TRP (transient receptor potential) melastatin 2] that belongs to the TRP family of ion channels.

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