Changes in either Cytosolic or Nucleoplasmic Inositol 1,4,5-Trisphosphate Levels Can Control Nuclear Ca2+ Concentration

Hennager, Daniel J.; Welsh, Michael J.; Delisle, Sylvain

doi:10.1074/jbc.270.10.4959

Cited by 99 publications

(61 citation statements)

References 25 publications

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“…Moreover, several lines of evidence (3)(4)(5)(6) suggest that increases in Ca 2ϩ in the nucleus have specific biological effects that differ from the effects of increases in cytosolic Ca 2ϩ . Studies in rat basophilic leukemia and HeLa cell lines suggest that nuclear Ca 2ϩ passively follows cytosolic Ca 2ϩ (7,8), although studies in Xenopus oocytes and in isolated hepatocyte nuclei suggest instead that nuclei are competent to generate their own Ca 2ϩ signals (9,10). Thus, it remains unclear whether or how Ca 2ϩ signaling within the nucleus is regulated.…”

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confidence: 94%

Nuclear and cytosolic calcium are regulated independently

Leite

Thrower

Echevarria

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

191

166

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Nuclear calcium (Ca 2؉ ) regulates a number of important cellular processes, including gene transcription, growth, and apoptosis. However, it is unclear whether Ca 2؉ signaling is regulated differently in the nucleus and cytosol. To investigate this possibility, we examined subcellular mechanisms of Ca 2؉ release in the HepG2 liver cell line. The type II isoform of the inositol 1,4,5-trisphosphate (InsP 3) receptor (InsP 3R) was expressed to a similar extent in the endoplasmic reticulum and nucleus, whereas the type III InsP 3R was concentrated in the endoplasmic reticulum, and the type I isoform was not expressed. Ca 2؉ signals induced by low InsP3 concentrations started earlier or were larger in the nucleus than in the cytosol, indicating higher sensitivity of nuclear Ca 2؉ stores for InsP3. Nuclear InsP3R channels were active at lower InsP 3 concentrations than InsP3R from cytosol. Enriched expression of type II InsP 3R in the nucleus results in greater sensitivity of the nucleus to InsP 3, thus providing a mechanism for independent regulation of Ca 2؉ -dependent processes in this cellular compartment.

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mentioning

confidence: 94%

Nuclear and cytosolic calcium are regulated independently

Leite

Thrower

Echevarria

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

191

166

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“…Release of Ca 2+ from intracellular stores is also mediated by several different types of Ca 2+ channel, of which InsP 3 Rs (see Box 2) and RyRs are the best characterised. (Hennager et al, 1995;Huh et al, 2007;Santella et al, 2003), direct visualisation of InsP 3 -evoked nuclear Ca 2+ signals (Higazi et al, 2009), reconstitution of nuclear InsP 3 Rs into lipid bilayers and prevention of nuclear Ca 2+ signals by using InsP 3 R antagonists (Kumar et al, 2008). Furthermore, the addition of InsP 3 to nuclei that were isolated from Xenopus oocytes, Aplysia neurons, mammalian epithelial cells or pancreatic acinar cells (Bezin et al, 2008a;Gerasimenko et al, 1995;Quesada and Verdugo, 2005;Stehno-Bittel et al, 1995) has been shown to induce nucleoplasmic Ca 2+ transients.…”

Section: Insp 3 Rs Ryrs and Naadprsmentioning

confidence: 99%

An update on nuclear calcium signalling

Bootman

Fearnley

Smyrnias

et al. 2009

Journal of Cell Science

189

194

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Over the past 15 years or so, numerous studies have sought to characterise how nuclear calcium (Ca 2+ ) signals are generated and reversed, and to understand how events that occur in the nucleoplasm influence cellular Ca 2+ activity, and vice versa. In this Commentary, we describe mechanisms of nuclear Ca 2+ signalling and discuss what is known about the origin and physiological significance of nuclear Ca 2+ transients. In particular, we focus on the idea that the nucleus has an autonomous Ca 2+ signalling system that can generate its own Ca 2+ transients that modulate processes such as gene transcription. We also discuss the role of nuclear pores and the nuclear envelope in controlling ion flux into the nucleoplasm. Journal of Cell Science 2338(which would cause its nuclear export) and through a physical interaction that occludes a nuclear-export sequence (NES) in the NFAT protein.An example of a nuclear-localised transcription factor that is regulated by both nuclear and cytosolic Ca 2+ signals is cyclic AMP response element-binding protein (CREB). The signalling mechanisms that underlie CREB activation have been worked out particularly well in neurons, in which it has been established that depolarisation leads to the rapid phosphorylation of CREB on Ser133 by Ca 2+ -calmodulin-dependent kinase IV, which provides a necessary, but not sufficient, signal for CREB-mediated gene transcription (Dolmetsch et al., 2001). The triggering event is an increase in cytosolic Ca 2+ levels in the immediate vicinity of L-type Ca 2+ channels or N-methyl-D-aspartate receptors that are found in the synapse, at a site that is distal to the nucleus (Shaywitz and Greenberg, 1999). As CREB is only found in the nucleus, the phosphorylation of Ser133 is mediated by one of several Ca 2+ -sensitive signal transduction cascades that convey information from the remote synapses into the nucleus. In the nucleus, phosphorylated CREB binds additional proteins to form a transcriptionally active complex (Shaywitz and Greenberg, 1999). Although the synaptic Ca 2+ signal does not need to propagate to the nucleus to induce phosphorylation of Ser133 on CREB, an increase in the level of nuclear Ca 2+ is required for CREB-mediated gene transcription to occur. This is because additional Ca 2+ -dependent phosphorylation of CREB and its co-activators is required (Chawla et al., 1998;Kornhauser et al., 2002). Indeed, nuclear injection of an artificial Ca 2+ buffer prevents CREB-mediated gene transcription, but not transcription induced by the serum-response element, which is sensitive to cytosolic Ca 2+ buffering (Hardingham et al., 1997).Another well-known target of nuclear Ca 2+ signalling is the transcriptional regulator downstream regulatory element antagonist modulator (DREAM). It is well established that DREAM represses the expression of prodynorphin, an opiate-receptor precursor, and that mice that lack DREAM have a constitutive analgesic condition (Cheng et al., 2002). DREAM contains four Ca 2+ -binding EF hands (a widely expressed structural mo...

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“…Evidence has been accumulating demonstrating that calcium movement, in and out of the nucleus, is a regulated process. It is agreed that ATP [11,17,20] and InsP4 [12,34] mediate external calcium entry into the nucleus, presumably into the nuclear envelope. The InsPs releases calcium from the nuclear envelope to the nuclear matrix [13,19,20].…”

Section: Discussionmentioning

confidence: 99%

“…It is agreed that ATP [11,17,20] and InsP4 [12,34] mediate external calcium entry into the nucleus, presumably into the nuclear envelope. The InsPs releases calcium from the nuclear envelope to the nuclear matrix [13,19,20]. In the study reported here we document that NAD (also other analogues) was able to induce calcium entry to the nuclei.…”

Section: Discussionmentioning

confidence: 99%

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Calcium transported to isolated rat liver nuclei by nicotinamide adenine dinucleotide is insensitive to thapsigargin

Matter

Malviya

1996

FEBS Letters

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Calcium uptake by isolated nuclei was mediated by nicotinamide adenhre dhmcleotide. Oxidized nicotinamide nucleotide analogues were more effective mediators of nuclear calcium uptake. Tbapsigargln inhibited ATP-mediated nuclear calcium transport without affecting NAD-mediated nuclear calcium uptake. Whilst DBHQ did not influence ATP-induced calcium transport, it did stimulate NAD-mediated nuclear calcium entry. Calcium channel blockers did not influence the action of NAD. This study provides a further mechanism for nuclear calcium transport regulated by changes in the cytosolic NAD+/NADH ratio.

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Changes in either Cytosolic or Nucleoplasmic Inositol 1,4,5-Trisphosphate Levels Can Control Nuclear Ca2+ Concentration

Cited by 99 publications

References 25 publications

Nuclear and cytosolic calcium are regulated independently

Nuclear and cytosolic calcium are regulated independently

An update on nuclear calcium signalling

Calcium transported to isolated rat liver nuclei by nicotinamide adenine dinucleotide is insensitive to thapsigargin

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