Entry
Name
Calcium signaling pathway - Nothobranchius furzeri (turquoise killifish)
Description
Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs).
The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it.
The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM).
Class
Environmental Information Processing; Signal transduction
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Nothobranchius furzeri (turquoise killifish) [GN:
nfu ]
Gene
107390594 gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632 ]
107385351 guanine nucleotide-binding protein G(s) subunit alpha-like isoform X1 [KO:K04632 ]
107396846 guanine nucleotide-binding protein G(olf) subunit alpha-like isoform X1 [KO:K04633 ]
107383531 gnal; guanine nucleotide-binding protein G(olf) subunit alpha isoform X1 [KO:K04633 ]
107387985 sarcoplasmic reticulum histidine-rich calcium-binding protein-like [KO:K23450 ]
107393664 calcium release-activated calcium channel protein 1-like [KO:K16056 ]
107373313 orai1; calcium release-activated calcium channel protein 1 [KO:K16056 ]
107385235 cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
107390617 cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
107385116 voltage-dependent L-type calcium channel subunit alpha-1D-like isoform X1 [KO:K04851 ]
107391407 voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04853 ]
107390498 cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
107390862 cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
107391184 cacna1a; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344 ]
107376625 voltage-dependent P/Q-type calcium channel subunit alpha-1A-like isoform X1 [KO:K04344 ]
107397069 voltage-dependent N-type calcium channel subunit alpha-1B-like isoform X1 [KO:K04849 ]
107375116 voltage-dependent N-type calcium channel subunit alpha-1B-like [KO:K04849 ]
107383886 voltage-dependent R-type calcium channel subunit alpha-1E-like isoform X1 [KO:K04852 ]
107393140 voltage-dependent R-type calcium channel subunit alpha-1E-like isoform X1 [KO:K04852 ]
107387548 voltage-dependent T-type calcium channel subunit alpha-1G-like [KO:K04854 ]
107376712 voltage-dependent T-type calcium channel subunit alpha-1H-like [KO:K04855 ]
107372838 voltage-dependent T-type calcium channel subunit alpha-1I-like isoform X1 [KO:K04856 ]
107376164 voltage-dependent T-type calcium channel subunit alpha-1I-like [KO:K04856 ]
107391375 voltage-dependent T-type calcium channel subunit alpha-1I-like [KO:K04856 ]
107381761 chrna7; neuronal acetylcholine receptor subunit alpha-7 [KO:K04809 ]
107379599 neuronal acetylcholine receptor subunit alpha-7-like isoform X1 [KO:K04809 ]
107382198 glutamate receptor ionotropic, NMDA 2B-like isoform X1 [KO:K05210 ]
107394013 gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
107392134 guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634 ]
107374739 guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634 ]
107374742 guanine nucleotide-binding protein subunit alpha-11-like isoform X1 [KO:K04634 ]
107393186 guanine nucleotide-binding protein subunit alpha-11 isoform X1 [KO:K04635 ]
107394012 guanine nucleotide-binding protein subunit alpha-14-like [KO:K04636 ]
107393185 guanine nucleotide-binding protein subunit alpha-11-like [KO:K04637 ]
107373888 platelet-derived growth factor subunit A-like isoform X1 [KO:K04359 ]
107395144 LOW QUALITY PROTEIN: fibroblast growth factor 17-like [KO:K04358 ]
107378043 vegfa; vascular endothelial growth factor A isoform X1 [KO:K05448 ]
107381684 figf; vascular endothelial growth factor D isoform X1 [KO:K05449 ]
107373767 gdnf; glial cell line-derived neurotrophic factor isoform X1 [KO:K05452 ]
107382825 plcd1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 isoform X1 [KO:K05857 ] [EC:3.1.4.11 ]
107384265 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1-like isoform X1 [KO:K05857 ] [EC:3.1.4.11 ]
107395431 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4-like isoform X1 [KO:K05857 ] [EC:3.1.4.11 ]
107378111 plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
107389305 plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859 ] [EC:3.1.4.11 ]
107387902 plce1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 isoform X1 [KO:K05860 ] [EC:3.1.4.11 ]
107385796 itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
107391515 itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960 ]
107386835 vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
107387551 voltage-dependent anion-selective channel protein 2-like [KO:K15040 ]
107396040 voltage-dependent anion-selective channel protein 2-like isoform X1 [KO:K15041 ]
107394258 vdac3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041 ]
107390564 troponin C, slow skeletal and cardiac muscles-like isoform X1 [KO:K05865 ]
107380364 phkg1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871 ] [EC:2.7.11.19 ]
107377008 phka1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190 ]
107381696 phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190 ]
107390263 serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform-like isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
107386394 serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform-like isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
107380138 serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform-like isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
107393481 serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform-like isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
107378925 nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
107394905 nuclear factor of activated T-cells, cytoplasmic 1-like [KO:K04446 ]
107390454 nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
107385406 nuclear factor of activated T-cells, cytoplasmic 2-like [KO:K17332 ]
107388393 nuclear factor of activated T-cells, cytoplasmic 3-like [KO:K17333 ]
107381886 nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
107383484 nfatc4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334 ]
107385307 pde1b; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B [KO:K13755 ] [EC:3.1.4.17 ]
107383797 calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A-like isoform X1 [KO:K13755 ] [EC:3.1.4.17 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C06124 Sphingosine 1-phosphate
C11556 1-Phosphatidyl-1D-myo-inositol 3,5-bisphosphate
C13051 Nicotinic acid adenine dinucleotide phosphate
Reference
Authors
Berridge MJ, Bootman MD, Roderick HL.
Title
Calcium signalling: dynamics, homeostasis and remodelling.
Journal
Reference
Authors
Berridge MJ, Lipp P, Bootman MD.
Title
The versatility and universality of calcium signalling.
Journal
Reference
Authors
Wang MC, Dolphin A, Kitmitto A.
Title
L-type voltage-gated calcium channels: understanding function through structure.
Journal
Reference
Authors
Ferrier GR, Howlett SE.
Title
Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction.
Journal
Reference
Authors
Keef KD, Hume JR, Zhong J.
Title
Regulation of cardiac and smooth muscle Ca(2+) channels (Ca(V)1.2a,b) by protein kinases.
Journal
Reference
Authors
Hell JW, Appleyard SM, Yokoyama CT, Warner C, Catterall WA.
Title
Differential phosphorylation of two size forms of the N-type calcium channel alpha 1 subunit which have different COOH termini.
Journal
J Biol Chem 269:7390-6 (1994)
Reference
Authors
Yunker AM.
Title
Modulation and pharmacology of low voltage-activated ("T-Type") calcium channels.
Journal
Reference
Authors
Yakel JL.
Title
Calcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription.
Journal
Reference
Authors
Fukunaga K, Miyamoto E.
Title
A working model of CaM kinase II activity in hippocampal long-term potentiation and memory.
Journal
Reference
Authors
Della Rocca GJ, van Biesen T, Daaka Y, Luttrell DK, Luttrell LM, Lefkowitz RJ.
Title
Ras-dependent mitogen-activated protein kinase activation by G protein-coupled receptors. Convergence of Gi- and Gq-mediated pathways on calcium/calmodulin, Pyk2, and Src kinase.
Journal
Reference
Authors
Furuichi T, Mikoshiba K.
Title
Inositol 1, 4, 5-trisphosphate receptor-mediated Ca2+ signaling in the brain.
Journal
Reference
Authors
Bruce JI, Straub SV, Yule DI.
Title
Crosstalk between cAMP and Ca2+ signaling in non-excitable cells.
Journal
Reference
Authors
Lee HC, Munshi C, Graeff R.
Title
Structures and activities of cyclic ADP-ribose, NAADP and their metabolic enzymes.
Journal
Reference
Authors
Crompton M.
Title
Mitochondrial intermembrane junctional complexes and their role in cell death.
Journal
Reference
Authors
Grewal SS, York RD, Stork PJ.
Title
Extracellular-signal-regulated kinase signalling in neurons.
Journal
Reference
Authors
Trushin SA, Pennington KN, Carmona EM, Asin S, Savoy DN, Billadeau DD, Paya CV.
Title
Protein kinase Calpha (PKCalpha) acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T lymphocytes.
Journal
Reference
Authors
Hutchins JR, Dikovskaya D, Clarke PR.
Title
Regulation of Cdc2/cyclin B activation in Xenopus egg extracts via inhibitory phosphorylation of Cdc25C phosphatase by Ca(2+)/calmodulin-dependent protein [corrected] kinase II.
Journal
Reference
Authors
Tornquist K
Title
Sphingosine 1-phosphate, sphingosine kinase and autocrine calcium signalling in thyroid cells.
Journal
Reference
Authors
Feske S
Title
Immunodeficiency due to defects in store-operated calcium entry.
Journal
Reference
Authors
Giachini FR, Lima VV, Hannan JL, Carneiro FS, Webb RC, Tostes RC
Title
STIM1/Orai1-mediated store-operated Ca2+ entry: the tip of the iceberg.
Journal
Reference
Authors
Baba Y, Kurosaki T
Title
[Regulation of store-operated calcium entry by STIM1].
Journal
Seikagaku 80:1123-8 (2008)
Reference
Authors
Galione A, Evans AM, Ma J, Parrington J, Arredouani A, Cheng X, Zhu MX
Title
The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca(2+) release channels.
Journal
Reference
Authors
Beard NA, Wei L, Dulhunty AF
Title
Ca(2+) signaling in striated muscle: the elusive roles of triadin, junctin, and calsequestrin.
Journal
Reference
Authors
Marty I
Title
Triadin regulation of the ryanodine receptor complex.
Journal
Reference
Authors
Arvanitis DA, Vafiadaki E, Sanoudou D, Kranias EG
Title
Histidine-rich calcium binding protein: the new regulator of sarcoplasmic reticulum calcium cycling.
Journal
Related pathway
nfu04070 Phosphatidylinositol signaling system
KO pathway
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