Dynamic regulation of IP3 receptor clustering and activity by IP3

Rahman, Taufiq; Taylor, Colin W.

doi:10.4161/chan.3.4.9247

Cited by 38 publications

(33 citation statements)

References 27 publications

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“…All of these led to the suggestion that the critical trigger for IP 3 R clustering was IP 3 binding to IP 3 Rs followed by the necessity of the subsequent conformational transition of these channels to their open state [15,18]. We found that IP 3 Rs recorded from the outer nuclear membranes of DT40 cells expressing recombinant IP 3 Rs (isoform 1 and 3) are initially randomly distributed, but a low [IP 3 ] (lower than required to maximally activate them, <300 nM) rapidly and reversibly drive these receptors into small clusters [22,23]. The molecular driving force of IP 3 R clustering is hitherto unknown.…”

Section: What Prompts Ip 3 Rs To Cluster?mentioning

confidence: 84%

“…The prevailing view is thus in favour of IP 3 Rs existing as pre-formed static clusters in the ER membrane and within each cluster, IP 3 Rs are stimulated by CICR initiated by a Ca 2 + blip. Our results have led us to suggest that IP 3 Rs may assemble 'on demand' into clusters in response to IP 3 and the process is dynamically regulated [22,23].…”

Section: Introductionmentioning

confidence: 83%

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Dynamic clustering of IP3 receptors by IP3

Rahman

2012

Biochemical Society Transactions

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The versatility of Ca2+ as an intracellular messenger stems largely from the impressive, but complex, spatiotemporal organization of the Ca2+ signals. For example, the latter when initiated by IP3 (inositol 1,4,5-trisphosphate) in many cells manifest hierarchical recruitment of elementary Ca2+ release events ('blips' and then 'puffs') en route to global regenerative Ca2+ waves as the cellular IP3 concentration rises. The spacing of IP3Rs (IP3 receptors) and their regulation by Ca2+ are key determinants of these spatially organized Ca2+ signals, but neither is adequately understood. IP3Rs have been proposed to be pre-assembled into clusters, but their composition, geometry and whether clustering affects IP3R behaviour are unknown. Using patch-clamp recording from the outer nuclear envelope of DT40 cells expressing rat IP3R1 or IP3R3, we have recently shown that low concentrations of IP3 cause IP3Rs to aggregate rapidly and reversibly into small clusters of approximately four IP3Rs. At resting cytosolic Ca2+ concentrations, clustered IP3Rs open independently, but with lower open probability, shorter open duration and lesser IP3-sensitivity than lone IP3Rs. This inhibitory influence of clustering on IP3R is reversed when the [Ca2+]i (cytosolic free Ca2+ concentration) increases. The gating of clustered IP3Rs exposed to increased [Ca2+]i is coupled: they are more likely to open and close together, and their simultaneous openings are prolonged. Dynamic clustering of IP3Rs by IP3 thus exposes them to local Ca2+ rises and increases their propensity for a CICR (Ca2+-induced Ca2+ rise), thereby facilitating hierarchical recruitment of the elementary events that underlie all IP3-evoked Ca2+ signals.

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Section: What Prompts Ip 3 Rs To Cluster?mentioning

confidence: 84%

Section: Introductionmentioning

confidence: 83%

Dynamic clustering of IP3 receptors by IP3

Rahman

2012

Biochemical Society Transactions

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“…This may facilitate (i) local elevation of luminal [Ca 2+ ] in jSR; and (ii) accumulation of molecules, including Ca 2+ , Na + (Blaustein et al, 2002;Poburko et al, 2008), and IP3, in the cytosolic microvolume from which the diffusion into the bulk cytoplasm is markedly restricted (Poburko et al, 2008). Taking this into account, the following factors may favour activation of IP3Rs by Ca 2+ influx: (i) a robust increase in [Ca 2+ ]i in the junctional cytosolic microvolume (Blaustein et al, 2002;Poburko et al, 2008); (ii) spontaneous basal activity of PLC (Prestwich and Bolton, 1991;Gordienko and Bolton, 2002;Horowitz et al, 2005;Peng et al, 2007); (iii) Ca 2+ activation of type 1 IP3Rs with positive co-operativity (Foskett et al, 2007); (iv) regulation of IP3Rs by the SR luminal [Ca 2+ ] (Rainbow et al, 2009);and (v) IP3R clustering (Rahman and Taylor, 2009).…”

Section: Figurementioning

confidence: 99%

Ca²⁺ entry following P2X receptor activation induces IP₃ receptor‐mediated Ca²⁺ release in myocytes from small renal arteries

Povstyan

Harhun

Gordienko

2011

British J Pharmacology

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BACKGROUND AND PURPOSEP2X receptors mediate sympathetic control and autoregulation of the renal circulation triggering contraction of renal vascular smooth muscle cells (RVSMCs) via an elevation of intracellular Ca 2+ concentration ([Ca 2+ ]i). Although it is well-appreciated that the myocyte Ca 2+ signalling system is composed of microdomains, little is known about the structure of the [Ca 2+ ]i responses induced by P2X receptor stimulation in vascular myocytes. EXPERIMENTAL APPROACHESUsing confocal microscopy, perforated-patch electrical recordings, immuno-/organelle-specific staining, flash photolysis and RT-PCR analysis we explored, at the subcellular level, the Ca 2+ signalling system engaged in RVSMCs on stimulation of P2X receptors with the selective agonist ab-methylene ATP (ab-meATP). KEY RESULTSRT-PCR analysis of single RVSMCs showed the presence of genes encoding inositol 1,4,5-trisphosphate receptor type 1(IP3R1) and ryanodine receptor type 2 (RyR2). The amplitude of the [Ca 2+ ]i transients depended on ab-meATP concentration. Depolarization induced by 10 mmol·L -1 ab-meATP triggered an abrupt Ca 2+ release from sub-plasmalemmal ('junctional') sarcoplasmic reticulum enriched with IP3Rs but poor in RyRs. Depletion of calcium stores, block of voltage-gated Ca 2+ channels (VGCCs) or IP3Rs suppressed the sub-plasmalemmal [Ca 2+ ]i upstroke significantly more than block of RyRs. The effect of calcium store depletion or IP3R inhibition on the sub-plasmalemmal [Ca 2+ ]i upstroke was attenuated following block of VGCCs. CONCLUSIONS AND IMPLICATIONSDepolarization of RVSMCs following P2X receptor activation induces IP3R-mediated Ca 2+ release from sub-plasmalemmal ('junctional') sarcoplasmic reticulum, which is activated mainly by Ca 2+ influx through VGCCs. This mechanism provides convergence of signalling pathways engaged in electromechanical and pharmacomechanical coupling in renal vascular myocytes. Abbreviations2-APB, 2-aminoethoxydiphenyl borate; ab-meATP, ab-methylene ATP; CICR, Ca 2+ -induced Ca 2+ release; CPA, cyclopiazonic acid; IP3, inositol 1,4,5-trisphosphate; IP3R, inositol 1,4,5-trisphosphate receptor; jSR, sub-plasmalemmal ('junctional') sarcoplasmic reticulum; MRS2578, N,N' NF279, 8,] bis(1,3,5-naphthalene-trisulphonic acid); PLC, phospholipase C; RBF, renal blood flow; RSNA, renal sympathetic nerve activity; RT-PCR, reverse transcription polymerase chain reaction; RVSMC, renal vascular smooth muscle cells; RyR, ryanodine receptor; SERCA, sarco-/endoplasmic reticulum Ca 2+ -ATPase; SPCU, sub-plasmalemmal [Ca 2+ ]i upstroke; SR, sarcoplasmic reticulum; U-73122, 1-[6-([(17b)-3-methoxyestra-1,3,5(10) IntroductionRenal blood flow (RBF) accounts for 20-25% of cardiac output at rest (Malpas and Leonard, 2000;Cupples and Braam, 2007). The mechanisms controlling contraction/relaxation of renal vascular smooth muscle cells (RVSMCs), which regulate the diameter of renal resistance arteries and hence RBF and glomerular filtration rate, play a fundamental role in the control of systemic blood pr...

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“…[Ca 2+ ] i is increased following Ca 2+ release from intracellular stores accomplished by the IP3 receptor [23]. The emptying of the intracellular stores is followed by activation of Ca 2+ release activated current I crac [24] leading to store operated Ca 2+ entry (SOCE) [25][26][27][28], which is accomplished by the pore forming Ca 2+ channel subunits Orai1, Orai2 or Orai3 [29][30][31][32][33] and their regulators STIM1 or STIM2 [34][35][36][37][38] …”

Section: Introductionmentioning

confidence: 99%

Impact of Janus Kinase 3 on Cellular Ca2+ Release, Store Operated Ca2+ Entry and Na+/Ca2+ Exchanger Activity in Dendritic Cells

Yan

Schmid

Hosseinzadeh

et al. 2015

Cell Physiol Biochem

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Background/Aims: Janus kinase 3 (JAK3), a tyrosine kinase mainly expressed in hematopoietic cells, participates in the signaling stimulating cell proliferation. The kinase is expressed in dendritic cells (DCs), antigen presenting cells involved in the initiation and regulation of antigen-specific T-cell responses. Dendritic cell function is regulated by cytosolic Ca²⁺ activity ([Ca²⁺]_i). Mediators increasing [Ca²⁺]_i in DCs include ATP and the chemokine receptor CXCR4 ligand CXCL12. The present study explored, whether JAK3 participates in the regulation of [Ca²⁺]_i in DCs. Methods: Fura-2 fluorescence was employed to determine [Ca²⁺]_i, and whole cell patch clamp to decipher electrogenic transport in immature DCs isolated from bone marrow of JAK3-knockout (jak3^-/-) or wild-type mice (jak3^+/+). Results: Without treatment, [Ca²⁺]_i was similar in jak3^-/- and jak3^+/+ DCs. Addition of ATP (100 µM) was followed by transient increase of [Ca²⁺]_i reflecting Ca²⁺ release from intracellular stores, an effect significantly less pronounced in jak3^-/- DCs than in jak3^+/+ DCs. CXCL12 administration was followed by a sustained increase of [Ca²⁺]_i reflecting receptor operated Ca²⁺ entry, an effect significantly less rapid in jak3^-/- DCs than in jak3^+/+ DCs. In addition, the Ca²⁺ release-activated Ca²⁺ channel (CRAC) current triggered by IP₃-induced Ca²⁺ store depletion and CXCL12 was significantly higher in DCs from jak3^+/+ mice than in jak3^-/- mice. Inhibition of sarcoendoplasmatic reticulum Ca²⁺-ATPase (SERCA) by thapsigargin (1 µM) in the absence of extracellular Ca²⁺ was followed by a transient increase of [Ca²⁺]_i reflecting Ca²⁺ release from intracellular stores, and subsequent readdition of extracellular Ca²⁺ in the continued presence of thapsigargin was followed by a sustained increase of [Ca²⁺]_i reflecting store operated Ca²⁺ entry (SOCE). Both, Ca²⁺ release from intracellular stores and SOCE were again significantly lower in jak3^-/- DCs than in jak3^+/+ DCs. Pretreatment of jak3^+/+ DCs with JAK inhibitor WHI-P154 (22 µM, 10 minutes or 24 hours) significantly blunted both thapsigargin induced Ca²⁺ release and subsequent SOCE. Abrupt replacement of Na⁺ containing (130 mM) and Ca²⁺ free (0 mM) extracellular bath by Na⁺ free (0 mM) and Ca²⁺ containing (2 mM) extracellular bath increased [Ca²⁺]_i reflecting Na⁺/Ca²⁺ exchanger activity, an effect again significantly less pronounced in jak3^-/- DCs than in jak3^+/+DCs. Conclusions: JAK3 defi...

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Dynamic regulation of IP3 receptor clustering and activity by IP3

Cited by 38 publications

References 27 publications

Dynamic clustering of IP3 receptors by IP3

Dynamic clustering of IP3 receptors by IP3

Ca²⁺ entry following P2X receptor activation induces IP₃ receptor‐mediated Ca²⁺ release in myocytes from small renal arteries

Impact of Janus Kinase 3 on Cellular Ca2+ Release, Store Operated Ca2+ Entry and Na+/Ca2+ Exchanger Activity in Dendritic Cells

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Dynamic regulation of IP3 receptor clustering and activity by IP3

Cited by 38 publications

References 27 publications

Dynamic clustering of IP3 receptors by IP3

Dynamic clustering of IP3 receptors by IP3

Ca2+ entry following P2X receptor activation induces IP3 receptor‐mediated Ca2+ release in myocytes from small renal arteries

Impact of Janus Kinase 3 on Cellular Ca2+ Release, Store Operated Ca2+ Entry and Na+/Ca2+ Exchanger Activity in Dendritic Cells

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Ca²⁺ entry following P2X receptor activation induces IP₃ receptor‐mediated Ca²⁺ release in myocytes from small renal arteries