Ca
            <sup>2+</sup>
            Entry Through Plasma Membrane IP
            <sub>3</sub>
            Receptors

Dellis, Olivier; Dedos, Skarlatos G.; Tovey, Stephen C.; Taufiq-Ur-Rahman,; Dübel, Stefan; Taylor, Colin W.

doi:10.1126/science.1125203

Cited by 170 publications

(208 citation statements)

References 27 publications

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“…This model for the IP 3 R pore, where TMD5 (the outer helix) and TMD6 (inner helix) cradle a short pore helix and selectivity filter (Fig. 2C), is consistent with mutagenesis of residues within this region affecting ion permeation (Boehning et al 2001b;Dellis et al 2006;Dellis et al 2008;Schug et al 2008), with biophysical evidence that the narrowest region of the pore lies close to the luminal entrance of the RyR and with the intermediate resolution structures of the pore region of RyR1 (Samso et al 2009). A conserved acidic residue (D2550 in IP 3 R1) at the luminal end of the selectivity filter (Fig.…”

Section: Structural Determinants Of Ip 3 R Activationmentioning

confidence: 52%

“…IP 3 R subtypes differ in their affinities for IP 3 , with the general consensus being that IP 3 R2 is more sensitive than IP 3 R1, and both are considerably more sensitive than IP 3 R3 (Tu et al 2005b;Iwai et al 2007). In the cellular context, however, differences in expression level (Dellis et al 2006;Tovey et al 2010), subcellular distribution (Petersen et al 1999), post-transcriptional and post-translational modifications, and association of IP 3 R with accessory proteins (Patterson et al 2004) may be more important determinants of sensitivity.…”

Section: Regulation Of Ip 3 Receptors By Ca 2þ and Ipmentioning

confidence: 99%

“…These came with elaboration of the pathways linking empty Ca 2þ stores to Ca 2þ entry, the so-called storeoperated Ca 2þ entry pathway (Putney 1997;Park et al 2009), and recognition that many trp channels are regulated by products of PLC activity (Nilius et al 2007). IP 3 receptors (IP 3 R) also contribute more directly to Ca 2þ entry across the plasma membrane either because, at least in some cells, IP 3 R are functionally expressed in the plasma membrane (Dellis et al 2006;Dellis et al 2008), or perhaps through their direct interactions with other plasma membrane Ca 2þ channels (Kiselyov et al 1999). Here, we focus solely on Ca 2þ release from the endoplasmic reticulum (ER) by IP 3 R. Some of the key steps in the evolution of our current understanding of IP 3 R are listed in Table 1.…”

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confidence: 99%

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IP3 Receptors: Toward Understanding Their Activation

Taylor¹,

Tovey²

2010

Cold Spring Harbor Perspectives in Biology

259

190

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Inositol 1,4,5-trisphosphate receptors (IP 3 R) and their relatives, ryanodine receptors, are the channels that most often mediate Ca 2þ release from intracellular stores. Their regulation by Ca 2þ allows them also to propagate cytosolic Ca 2þ signals regeneratively. This brief review addresses the structural basis of IP 3 R activation by IP 3 and Ca 2þ . IP 3 initiates IP 3 R activation by promoting Ca 2þ binding to a stimulatory Ca 2þ -binding site, the identity of which is unresolved. We suggest that interactions of critical phosphate groups in IP 3 with opposite sides of the clam-like IP 3 -binding core cause it to close and propagate a conformational change toward the pore via the adjacent N-terminal suppressor domain. The pore, assembled from the last pair of transmembrane domains and the intervening pore loop from each of the four IP 3 R subunits, forms a structure in which a luminal selectivity filter and a gate at the cytosolic end of the pore control cation fluxes through the IP 3 R.

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Section: Structural Determinants Of Ip 3 R Activationmentioning

confidence: 52%

Section: Regulation Of Ip 3 Receptors By Ca 2þ and Ipmentioning

confidence: 99%

mentioning

confidence: 99%

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IP3 Receptors: Toward Understanding Their Activation

Taylor¹,

Tovey²

2010

Cold Spring Harbor Perspectives in Biology

259

190

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“…Type 3 IP3 receptors have been identified on the surface of B cells, where they directly mediate Ca 2+ influx from the extracellular space. 51,52 Our immunocytochemistry analyses (unpublished data) showed these receptors to be expressed on the membranes of cDCs but not on those of macrophages, suggesting that they could, indeed, decide the fate of these two cell types.…”

Section: Apoptotic Death Of Cdcsmentioning

confidence: 99%

The dendritic cell life cycle

Granucci¹,

Zanoni²

2009

Cell Cycle

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D endritic cells (DCs) are a specialclass of leukocytes actively involved in initiating innate and adaptive immune responses against invading pathogens. They play a fundamental role in determining both the type and efficiency of adaptive immune reactions. In particular, the efficiency of adaptive responses is strictly correlated with the survival of the DCs that have encountered the antigen. In physiological conditions, the rapid death of DCs by apoptosis after an encounter with a microbe is important to prevent both aberrant activation and autoimmunity. The mechanism leading to DC apoptosis after exposure to lipopolysaccharide (LPS) was recently elucidated, with activation of the c2 and c3 isoforms of nuclear factor of activated T cells (NFAT) playing a particularly important role in this process. In particular, the exposure of DCs to LPS induces the activation of Src-family kinases and phospholipase C (PLC)γ2, the influx of extracellular Ca 2+ and calcineurin-dependent nuclear NFAT translocation. The initiation of this pathway is independent of TLR4 engagement and depends exclusively on CD14. We also consider here the possible role of CD14 in initiating this pathway and the way in which the c2 and c3 isoforms of NFAT exert their pro-apoptotic effects.

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“…Emptying the ER Ca 2þ stores triggers plasmalemmal store-operated Ca 2þ -entry, SOCE [128], which ubiquitously occurs in non-excitable cells [129,130]. Activation of SOCE involves intraluminal Ca 2þ -sensor (Stim) and an influx channel (Orai and associated proteins or TRPC channels) in the plasmalemma [131,132]. Although operational SOCE is well characterized in the ciliate, Paramecium [40], Orai and Stim have not been detected (as yet), in contrast to informatics data obtained from choanoflagellates [78] that are placed at the basis of metazoans.…”

Section: Intracellular Ca 2þ Fluxes and Ca 2þ Regulationmentioning

confidence: 99%

Inseparable tandem: evolution chooses ATP and Ca²⁺to control life, death and cellular signalling

Plattner

Verkhratsky

2016

Phil. Trans. R. Soc. B

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From the very dawn of biological evolution, ATP was selected as a multipurpose energy-storing molecule. Metabolism of ATP required intracellular free Ca 2þ to be set at exceedingly low concentrations, which in turn provided the background for the role of Ca 2þ as a universal signalling molecule. The early-eukaryote life forms also evolved functional compartmentalization and vesicle trafficking, which used Ca 2þ as a universal signalling ion; similarly, Ca 2þ is needed for regulation of ciliary and flagellar beat, amoeboid movement, intracellular transport, as well as of numerous metabolic processes. Thus, during evolution, exploitation of atmospheric oxygen and increasingly efficient ATP production via oxidative phosphorylation by bacterial endosymbionts were a first step for the emergence of complex eukaryotic cells. Simultaneously, Ca 2þ started to be exploited for shortrange signalling, despite restrictions by the preset phosphate-based energy metabolism, when both phosphates and Ca 2þ interfere with each other because of the low solubility of calcium phosphates. The need to keep cytosolic Ca 2þ low forced cells to restrict Ca 2þ signals in space and time and to develop energetically favourable Ca 2þ signalling and Ca 2þ microdomains. These steps in tandem dominated further evolution. The ATP molecule (often released by Ca 2þ -regulated exocytosis) rapidly grew to be the universal chemical messenger for intercellular communication; ATP effects are mediated by an extended family of purinoceptors often linked to Ca 2þ signalling. Similar to atmospheric oxygen, Ca 2þ must have been reverted from a deleterious agent to a most useful (intra-and extracellular) signalling molecule. Invention of intracellular trafficking further increased the role for Ca 2þ homeostasis that became critical for regulation of cell survival and cell death. Several mutually interdependent effects of Ca 2þ and ATP have been exploited in evolution, thus turning an originally unholy alliance into a fascinating success story.This article is part of the themed issue 'Evolution brings Ca 2þ and ATP together to control life and death'.

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Ca ²⁺ Entry Through Plasma Membrane IP ₃ Receptors

Cited by 170 publications

References 27 publications

IP3 Receptors: Toward Understanding Their Activation

IP3 Receptors: Toward Understanding Their Activation

The dendritic cell life cycle

Inseparable tandem: evolution chooses ATP and Ca²⁺to control life, death and cellular signalling

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Ca 2+ Entry Through Plasma Membrane IP 3 Receptors

Cited by 170 publications

References 27 publications

IP3 Receptors: Toward Understanding Their Activation

IP3 Receptors: Toward Understanding Their Activation

The dendritic cell life cycle

Inseparable tandem: evolution chooses ATP and Ca2+to control life, death and cellular signalling

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Ca ²⁺ Entry Through Plasma Membrane IP ₃ Receptors

Inseparable tandem: evolution chooses ATP and Ca²⁺to control life, death and cellular signalling