Functional consequences of activating store-operated CRAC channels

doi:10.1016/j.ceca.2007.02.012

Cell Calcium

Volume 42, Issue 2, August 2007, Pages 111-121

https://doi.org/10.1016/j.ceca.2007.02.012 Get rights and content

Abstract

Store-operated CRAC channels, which are activated by the emptying of the endoplasmic reticulum Ca²⁺ stores, are an important and widespread route for triggering rises in cytoplasmic Ca²⁺. The cellular responses that are activated in response to Ca²⁺ entry through CRAC channels are being dissected out, and recent evidence has established that CRAC channels can induce both short-term (safeguarding the Ca²⁺ content of the endoplasmic reticulum, maintenance of cytoplasmic Ca²⁺ oscillations, enzyme activation, secretion) and long-term (gene expression) changes in cells. CRAC channel activation is therefore capable of evoking a range of temporally distinct responses, highlighting the versatility of this ubiquitous Ca²⁺ entry pathway.

Section snippets

CRAC channels

Store-operated channels with distinct biophysical properties have been reported in different cell types, suggesting the existence of a store-operated channel family ([5]; Table 1). Nevertheless, the most widespread store-operated pathway and the most extensively studied one is the Ca²⁺ release-activated Ca²⁺ (CRAC) channel [5], [6], [7]. CRAC channels have certain hallmarks that readily discriminate them from other Ca²⁺ pathways. First, the channels are exquisitely selective for Ca²⁺, with no

Molecular identification of the CRAC channel system

After many years of investigation by a number of laboratories, the molecular basis of store-operated entry is now being unravelled. These recent advances are discussed in more detail elsewhere in this issue but I will briefly touch upon them as they are of relevance to the discussion of Ca²⁺ oscillations below. RNAi strategies identified the endoplasmic reticular membrane protein STIM1 as being the Ca²⁺ sensor that detects the fall in luminal Ca²⁺ content and which thus initiates the

Cellular responses activated by Ca²⁺ entry through CRAC channels

Although store-operated channels are widely expressed throughout the phylogenetic tree, until recently surprisingly little was known about their specific cellular roles. Most research effort has been dedicated to pursuing the molecular basis of store-operated entry, with the tacit understanding that a calcium entry pathway as ubiquitous as the store-operated one is likely to be of considerable physiological relevance. Moreover, there is a dearth of relatively specific pharmacological blockers

Ca²⁺ entry through CRAC channels repletes the ER with Ca²⁺

The ER is a multifarious organelle carrying out a range of interdependent processes [32]. In addition to its well-documented role as both an agonist-sensitive Ca²⁺ store and sink [33], other Ca²⁺-dependent processes take place within the lumen of the organelle. Foremost amongst these is protein folding/processing [32]. Numerous Ca²⁺-dependent luminal chaperone proteins ensure that newly synthesized proteins are folded correctly and then sent off to the appropriate destination. Protein

CRAC channels and cytoplasmic Ca² oscillations

In many non-excitable cell types, modest levels of receptor stimulation evoke cytoplasmic Ca²⁺ oscillations [50]. These often arise from regenerative Ca²⁺ release from intracellular Ca²⁺ stores. Important information is encoded in the amplitude/frequency of the oscillations and a range of cellular responses can be evoked by this form of Ca²⁺ signalling including exocytosis, mitochondrial ATP production and gene transcription [2].

Ca²⁺ oscillations gradually run down in the absence of

CRAC channels and enzyme activation

Store-operated Ca²⁺ influx in response to thapsigargin stimulation is an effective regulator of Ca²⁺-sensitive adenylate cyclases [72], thereby providing a link between the Ca²⁺ and cAMP signalling pathways. The activities of both Ca²⁺-stimulable and Ca²⁺-inhibitable cyclases are gated by Ca²⁺ entry but not by the preceding Ca²⁺ release phase [73], [74]. Moreover, stimulation of Ca²⁺ entry either by high concentrations of the Ca²⁺ ionophore ionomycin or through other Ca²⁺ influx pathways (e.g.

CRAC channels and gene transcription

In view of the fact that Ca²⁺ influx in non-excitable cells is an essential trigger for cell growth and proliferation, store-operated Ca²⁺ entry has long been implicated in regulation of gene transcription. Consistent with this, a study by Fanger et al. on mutant lymphocytes that were defective in I_CRAC established a close correlation between the reduction in Ca²⁺ influx due to defective I_CRAC and subsequent Ca²⁺-dependent gene transcription [85]. Furthermore, Dolmetsch et al. [86] showed that

Concluding remarks

Clearly, one key function of CRAC channels is to ensure the ER contains sufficient Ca²⁺ to maintain important Ca²⁺-dependent functions including protein folding, vesicle trafficking and regulation of apoptosis. Moreover, exploitation of the recent advances in the molecular basis of store-operated Ca²⁺ entry has established that CRAC channels are essential for supporting receptor-dependent Ca²⁺ oscillations and hence sculpt the spatial and temporal profile of intracellular Ca²⁺ signals. In

Acknowledgements

Work in my laboratory is funded by the Medical Research Council. I am grateful to Prof. Reinhold Penner for comments on the manuscript.

References (101)

D. Bakowski et al.
Permeation through store-operated CRAC channels in divalent-free solution: potential problems and implications for putative CRAC channel genes
Cell Calcium
(2002)
G.H. Rychkov et al.
Plasma membrane Ca²⁺ release-activated Ca²⁺ channels with a high selectivity for Ca²⁺ identified by patch-clamp recording in rat liver cells
Hepatology
(2001)
J. Liou et al.
STIM is a calcium sensor essential for calcium-store-depletion-triggered calcium infux
Curr. Biol.
(2005)
J.C. Mercer et al.
Large store-operated calcium-selective currents due to co-expression of Orai1 with the intracellular calcium sensor, STIM1
J. Biol. Chem.
(2006)
J. Soboloff et al.
Orai1 and STIM reconstitute store-operated calcium channel function
J. Biol. Chem.
(2006)
M. Vig et al.
CRACM1 multimers form the ion-selective pore of the CRAC channel
Curr. Biol.
(2006)
M.J. Berridge
The endoplasmic reticulum: a multifunctional signaling organelle
Cell Calcium
(2002)
A. Zweifach et al.
Slow calcium-dependent inactivation of depletion-activated calcium current
J. Biol. Chem.
(1995)
A.B. Parekh
Slow feedback inhibition of calcium release-activated calcium current by calcium entry
J. Biol. Chem.
(1998)
J.W. Putney
A model for receptor-regulated calcium entry
Cell Calcium
(1986)

H. Takemura et al.

Activation of calcium entry by the tumour promoter thapsigargin in parotid acinar cells. Evidence that an intracellular calcium pool and not an inositol phosphate regulates calcium fluxes at the plasma membrane

J. Biol. Chem.

(1989)

H. Mogami et al.

Ca²⁺ flow via tunnels in polarized cells: recharging of apical Ca²⁺ stores by focal Ca²⁺ entry through basal membrane patch

Cell

(1997)

S. Muallem et al.

The route of calcium entry during reloading of the intracellular calcium pool in pancreatic acini

J. Biol. Chem.

(1990)

O.H. Petersen et al.

The endoplasmic reticulum: one continuous or several separate Ca²⁺ stores

Trends Neurosci.

(2001)

G. Chernaya et al.

Sodium–calcium exchange and store-operated calcium influx in transfected Chinese hamster ovary cells expressing the bovine cardiac sodium–calcium exchanger

J. Biol. Chem.

(1996)

H.Y. Kim et al.

Chromatographic resolution of an intracellular calcium influx factor from thapsigargin-activated jurkats. Evidence for multiple activities influencing calcium elevation in Xenopus oocytes

J. Biol. Chem.

(1995)

T.J. Shuttleworth

What drives calcium entry during [Ca²⁺]_i oscillations? Challenging the capacitative model

Cell Calcium

(1999)

T.J. Shuttleworth

Arachidonic acid activates the noncapacitative entry of Ca²⁺ during Ca²⁺ oscillations

J. Biol. Chem.

(1996)

O. Mignen et al.

IARC, a novel arachidonate-regulated, noncapacitative Ca²⁺ entry channel

J. Biol. Chem.

(2000)

O. Mignen et al.

Permeation of monovalent cations through the non-capacitative arachidonate-regulated Ca²⁺ channels in HEK293 cells. Comparison with endogenous store-operated channels

J. Biol. Chem.

(2001)

O. Mignen et al.

Ca²⁺ selectivity and fatty acid specificity of the noncapacitative, arachidonate-regulated Ca²⁺ (ARC) channels

J. Biol. Chem.

(2003)

Y. Wang et al.

2-Aminoethoxydiphenyl borate inhibits phototransduction and blocks voltage-gated potassium channels in Limulus ventral photoreceptors

Cell Calcium

(2002)

L. Missiaen et al.

2-Aminoethoxydiphenyl borate affects the inositol 1,4,5-trisphosphate receptor, the intracellular Ca²⁺ pump and the non-specific Ca²⁺ leak from the non-mitochondrial Ca²⁺ stores in permeabilized A7r5 cells

Cell Calcium

(2001)

J.K. Foskett et al.

[Ca²⁺]_i inhibition of Ca release-activated Ca²⁺ influx underlies agonist-and thapsigargin-induced [Ca²⁺]_i oscillations in salivary acinar cells

J. Biol. Chem.

(1994)

L. Missiaen et al.

Kinetics of empty store-activated Ca²⁺ influx in HeLa cells

J. Biol. Chem.

(1994)

K.A. Fagan et al.

Functional co-localization of transfected Ca²⁺-stimulable adenylyl cyclases with capacitative Ca²⁺ entry sites

J. Biol. Chem.

(1996)

K.A. Fagan et al.

Dependence of the Ca²⁺-inhibitable adenyl cyclase of C6-2B glioma cells on capacitative Ca²⁺ entry

J. Biol. Chem.

(1998)

T.J. Shuttleworth et al.

Discriminating between capacitative and arachidonate-activated Ca²⁺ entry pathways in FEK293 cells

J. Biol. Chem.

(1999)

S. Lin et al.

Sustained endothelial nitric oxide-synthase activation requires capacitative Ca²⁺ entry

J. Biol. Chem.

(2000)

C.C. Leslie

Properties and regulation of cytosolic phospholipase A2

J. Biol. Chem.

(1997)

J.H. Evans et al.

Intracellular calcium signals regulating cytosolic phospholipase A2 translocation to internal membranes

J. Biol. Chem.

(2001)

S. Glover et al.

Translocation of the 85-kDa phospholipase A2 from cytosol to the nuclear envelope in rat basophilic leukemia cells stimulated with calcium ionophore or IgE/antigen

J. Biol. Chem.

(1995)

E.A. Nalefski et al.

Delineation of two functionally distinct domains of cytosolic phospholipase A2, a regulatory Ca(2+)-dependent lipid-binding domain and a Ca(2+)-independent catalytic domain

J. Biol. Chem.

(1994)

L.J. Reynolds et al.

Metal ion and salt effects on the phospholipase A2, lysophospholipase, and transacylase activities of human cytosolic phospholipase A2

Biochim. Biophys. Acta

(1993)

W.C. Chang et al.

Close functional coupling between CRAC channels, arachidonic acid release and leukotriene secretion

J. Biol. Chem.

(2004)

C. Fasolato et al.

A GTP-dependent step in the activation mechanism of capacitative calcium influx

J. Biol. Chem.

(1993)

E.S. Trepakova et al.

Calcium influx factor directly activates store-operated cation channels in vascular smooth muscle cells

J. Biol. Chem.

(2000)

R. Ma et al.

Protein kinase C activates store-operated calcium channels in human glomerular mesangial cells

J. Biol. Chem.

(2001)

E. Carafoli

Calcium signalling: a tale for all seasons

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

(2002)

M.J. Berridge et al.

Calcium signalling: dynamics, homeostasis and remodelling

Nat. Rev. Mol. Cell Biol.

(2003)

K. Venkatachalam et al.

The cellular and molecular basis of store-operated calcium entry

Nat. Cell Biol.

(2002)

A.B. Parekh et al.

Store-operated calcium channels

Physiol. Rev.

(2005)

A.B. Parekh et al.

Store-operated calcium influx

Physiol. Rev.

(1997)

M. Hoth et al.

Depletion of intracellular calcium stores activates a calcium current in mast cells

Nature

(1992)

A. Zweifach et al.

Mitogen-regulated Ca²⁺ current of T lymphocytes is activated by depletion of intracellular Ca²⁺ stores

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

(1993)

M. Hoth et al.

Calcium release-activated calcium current in rat mast cells

J. Physiol. (Lond.)

(1993)

L. Fierro et al.

Substantial depletion of the intracellular Ca²⁺ stores is required for macroscopic activation of the Ca²⁺ release-activated Ca²⁺ current in rat basophilic leukaemia cells

J. Physiol. (Lond.)

(2000)

M. Prakriya et al.

Separation and characterization of currents through store-operated CRAC channels and Mg²⁺-inhibited cation (MIC) channels

J. Gen. Physiol.

(2002)

M. Prakriya et al.

Regulation of CRAC channel activity by recruitment of silent channels to a high open-probability gating mode

J. Gen. Physiol.

(2006)

A. Zweifach et al.

Rapid inactivation of depletion-activated calcium current (ICRAC) due to local calcium feedback

J. Gen. Physiol.

(1995)

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Functional consequences of activating store-operated CRAC channels

Abstract

Section snippets

CRAC channels

Molecular identification of the CRAC channel system

Cellular responses activated by Ca2+ entry through CRAC channels

Ca2+ entry through CRAC channels repletes the ER with Ca2+

CRAC channels and cytoplasmic Ca2 oscillations

CRAC channels and enzyme activation

CRAC channels and gene transcription

Concluding remarks

Acknowledgements

Cell Calcium

Hepatology

Curr. Biol.

J. Biol. Chem.

J. Biol. Chem.

Curr. Biol.

Cell Calcium

J. Biol. Chem.

J. Biol. Chem.

Cell Calcium

J. Biol. Chem.

Cell

J. Biol. Chem.

Trends Neurosci.

J. Biol. Chem.

J. Biol. Chem.

Cell Calcium

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Cell Calcium

Cell Calcium

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Biochim. Biophys. Acta

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Calcium signalling: a tale for all seasons

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

Calcium signalling: dynamics, homeostasis and remodelling

Nat. Rev. Mol. Cell Biol.

The cellular and molecular basis of store-operated calcium entry

Nat. Cell Biol.

Store-operated calcium channels

Physiol. Rev.

Store-operated calcium influx

Physiol. Rev.

Depletion of intracellular calcium stores activates a calcium current in mast cells

Nature

Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores

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

Calcium release-activated calcium current in rat mast cells

J. Physiol. (Lond.)

Substantial depletion of the intracellular Ca2+ stores is required for macroscopic activation of the Ca2+ release-activated Ca2+ current in rat basophilic leukaemia cells

J. Physiol. (Lond.)

Separation and characterization of currents through store-operated CRAC channels and Mg2+-inhibited cation (MIC) channels

J. Gen. Physiol.

Regulation of CRAC channel activity by recruitment of silent channels to a high open-probability gating mode

J. Gen. Physiol.

Rapid inactivation of depletion-activated calcium current (ICRAC) due to local calcium feedback

J. Gen. Physiol.

Cellular responses activated by Ca²⁺ entry through CRAC channels

Ca²⁺ entry through CRAC channels repletes the ER with Ca²⁺

CRAC channels and cytoplasmic Ca² oscillations

Mitogen-regulated Ca²⁺ current of T lymphocytes is activated by depletion of intracellular Ca²⁺ stores

Substantial depletion of the intracellular Ca²⁺ stores is required for macroscopic activation of the Ca²⁺ release-activated Ca²⁺ current in rat basophilic leukaemia cells

Separation and characterization of currents through store-operated CRAC channels and Mg²⁺-inhibited cation (MIC) channels