Selective coupling of type 6 adenylyl cyclase with type 2 IP3 receptors mediates direct sensitization of IP3 receptors by cAMP

Tovey, Stephen C.; Dedos, Skarlatos G.; Taylor, Emily J. A.; Church, Jarrod E; Taylor, Colin W.

doi:10.1083/jcb.200803172

Cited by 93 publications

(178 citation statements)

References 57 publications

Supporting

Mentioning

161

Contrasting

Order By: Relevance

“…We Tovey et al, 2008;Tovey et al, 2003) and others (Schwindinger et al, 1998) find that in HEK 293 cells stably expressing physiological levels of PTHR1 (HEK-PR1 cells), PTH stimulates AC, but it does not alone evoke an increase in [Ca 2+ ] i . However, PTH (or endogenous b 2 -adrenoceptors) potentiates the Ca 2+ signals evoked by receptors that stimulate PLC (Kurian et al, 2009;Tovey et al, 2008). This effect of PTH is entirely mediated by cAMP, it requires activation of neither cAMP-dependent protein kinase (PKA) nor epacs, and it results from cAMP binding to IP 3 R directly or to a protein that tightly associates with IP 3 R (Tovey et al, 2008;Tovey et al, 2010).…”

Section: Introductionmentioning

confidence: 60%

“…Cyclic AMP (cAMP), via exchange protein activated by cAMP (epac) and the monomeric G protein Rap, can also stimulate PLCe (Schmidt et al, 2001). We Tovey et al, 2008;Tovey et al, 2003) and others (Schwindinger et al, 1998) find that in HEK 293 cells stably expressing physiological levels of PTHR1 (HEK-PR1 cells), PTH stimulates AC, but it does not alone evoke an increase in [Ca 2+ ] i . However, PTH (or endogenous b 2 -adrenoceptors) potentiates the Ca 2+ signals evoked by receptors that stimulate PLC (Kurian et al, 2009;Tovey et al, 2008).…”

Section: Introductionmentioning

confidence: 72%

See 1 more Smart Citation

Cyclic AMP directs IP3-evoked Ca2+ signalling to different intracellular Ca2+ stores

Tovey

Taylor

2013

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

SummaryCholesterol depletion reversibly abolishes carbachol-evoked Ca 2+ release from inositol (1,4,5)-trisphosphate (IP 3 )-sensitive stores, without affecting the distribution of IP 3 receptors (IP 3 R) or endoplasmic reticulum, IP 3 formation or responses to photolysis of caged IP 3 . Receptors that stimulate cAMP formation do not alone evoke Ca 2+ signals, but they potentiate those evoked by carbachol. We show that these potentiated signals are entirely unaffected by cholesterol depletion and that, within individual cells, different IP 3 -sensitive Ca 2+ stores are released by carbachol alone and by carbachol combined with receptors that stimulate cAMP formation. We suggest that muscarinic acetylcholine receptors in lipid rafts deliver IP 3 at high concentration to associated IP 3 R, stimulating them to release Ca 2+ . Muscarinic receptors outside rafts are less closely associated with IP 3 R and provide insufficient local IP 3 to activate IP 3 R directly. These IP 3 R, probably type 2 IP 3 R within a discrete Ca 2+ store, are activated only when their sensitivity is increased by cAMP. Sensitization of IP 3 R by cAMP extends the effective range of signalling by phospholipase C, allowing muscarinic receptors that are otherwise ineffective to recruit additional IP 3 -sensitive Ca 2+ stores.

show abstract

Section: Introductionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 72%

Cyclic AMP directs IP3-evoked Ca2+ signalling to different intracellular Ca2+ stores

Tovey

Taylor

2013

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…Measurements of [Ca 2+ ] i in HEK cells were performed at 20˚C in HBS (Tovey et al, 2008). HBS had the following composition: 135 mM NaCl, 5.9 mM KCl, 1.2 mM MgCl 2 , 1.5 mM CaCl 2 , 11.5 mM glucose, 11.6 mM HEPES, pH 7.3.…”

Section: + ] Imentioning

confidence: 99%

“…Fluo-4 fluorescence was calibrated to [Ca 2+ ] i using the equation: [Ca 2+ ] i 5K D (F2F min )/(F max 2F), using a K D for Ca 2+ of 345 nM. Fluorescence from Ca 2+ -saturated (F max ) and Ca 2+ free (F min ) fluo-4 was measured in adjacent wells by addition of Triton X-100 (0.1%) with CaCl 2 (10 mM) or BAPTA (10 mM) (Tovey et al, 2008).…”

Section: + ] Imentioning

confidence: 99%

“…Fluorescence, detected at .510 nm after alternating excitation at 340 and 380 nm, was detected using an Olympus IX71 inverted fluorescence microscope with a Luca electron multiplying charge-coupled device (EMCCD) camera (Andor Technology, Belfast, UK) with a 4061.35 NA objective and analysed using MetaFluor software (MDS Analytical Devices, Wokingham, UK). After correction for background fluorescence, fluorescence ratios (F 340 /F 380 ) were calibrated to [Ca 2+ ] i using Ca 2+ standard solutions (Tovey et al, 2008).…”

Section: + ] Imentioning

confidence: 99%

See 1 more Smart Citation

Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum

López-Sanjurjo

Tovey

Prole

et al. 2013

Journal of Cell Science

Self Cite

126

111

View full text Add to dashboard Cite

Summary Most intracellular Ca2+ signals result from opening of Ca 2+ channels in the plasma membrane or endoplasmic reticulum (ER), and they are reversed by active transport across these membranes or by shuttling Ca 2+ into mitochondria. Ca 2+ channels in lysosomes contribute to endo-lysosomal trafficking and Ca 2+ signalling, but the role of lysosomal Ca 2+ uptake in Ca 2+ signalling is unexplored. Inhibition of lysosomal Ca 2+ uptake by dissipating the H + gradient (using bafilomycin A 1 ), perforating lysosomal membranes (using glycyl-Lphenylalanine 2-naphthylamide) or lysosome fusion (using vacuolin) increased the Ca 2+ signals evoked by receptors that stimulate inositol 1,4,5-trisphosphate [Ins(1,4,5)P 3 ] formation. Bafilomycin A 1 amplified the Ca 2+ signals evoked by photolysis of caged Ins(1,4,5)P 3 or by inhibition of ER Ca 2+ pumps, and it slowed recovery from them. Ca 2+ signals evoked by store-operated Ca 2+ entry were unaffected by bafilomycin A 1 . Video-imaging with total internal reflection fluorescence microscopy revealed that lysosomes were motile and remained intimately associated with the ER. Close association of lysosomes with the ER allows them selectively to accumulate Ca 2+ released by Ins(1,4,5)P 3 receptors.

show abstract

Regulation of Multidrug Resistance-Associated Protein 2 by Calcium Signaling in Mouse Liver

et al. 2010

View full text Add to dashboard Cite

Multidrug resistance associated protein 2 (Mrp2) is a canalicular transporter responsible for organic anion secretion into bile. Mrp2 activity is regulated by insertion into the plasma membrane; however, the factors that control this are not understood. Calcium (Ca 21 ) signaling regulates exocytosis of vesicles in most cell types, and the type II inositol 1,4,5-triphosphate receptor (InsP 3 R2) regulates Ca 21 release in the canalicular region of hepatocytes. However, the role of InsP 3 R2 and of Ca 21 signals in canalicular insertion and function of Mrp2 is not known. The aim of this study was to determine the role of InsP 3 R2-mediated Ca 21 signals in targeting Mrp2 to the canalicular membrane. Livers, isolated hepatocytes, and hepatocytes in collagen sandwich culture from wild-type (WT) and InsP 3 R2 knockout (KO) mice were used for western blots, confocal immunofluorescence, and time-lapse imaging of Ca 21 signals and of secretion of a fluorescent organic anion. Plasma membrane insertion of green fluorescent protein (GFP)-Mrp2 expressed in HepG2 cells was monitored by total internal reflection microscopy. InsP 3 R2 was concentrated in the canalicular region of WT mice but absent in InsP 3 R2 KO livers, whereas expression and localization of InsP 3 R1 was preserved, and InsP 3 R3 was absent from both WT and KO livers. Ca 21 signals induced by either adenosine triphosphate (ATP) or vasopressin were impaired in hepatocytes lacking InsP 3 R2. Canalicular secretion of the organic anion 5-chloromethylfluorescein diacetate (CMFDA) was reduced in KO hepatocytes, as well as in WT hepatocytes treated with 1,2-bis(o-aminophenoxy)ethane-N,N,N 0 ,N 0 -tetraacetic acid (BAPTA). Moreover, the choleretic effect of tauroursodeoxycholic acid (TUDCA) was impaired in InsP 3 R2 KO mice. Finally, ATP increased GFP-Mrp2 fluorescence in the plasma membrane of HepG2 cells, and this also was reduced by BAPTA. Conclusion: InsP 3 R2-mediated Ca 21 signals enhance organic anion secretion into bile by targeting Mrp2 to the canalicular membrane. (HEPATOLOGY 2010;52:327-337)

show abstract

Selective coupling of type 6 adenylyl cyclase with type 2 IP3 receptors mediates direct sensitization of IP3 receptors by cAMP

Cited by 93 publications

References 57 publications

Cyclic AMP directs IP3-evoked Ca2+ signalling to different intracellular Ca2+ stores

Cyclic AMP directs IP3-evoked Ca2+ signalling to different intracellular Ca2+ stores

Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum

Regulation of Multidrug Resistance-Associated Protein 2 by Calcium Signaling in Mouse Liver

Contact Info

Product

Resources

About