Calcium signaling - wikipedia Calcium signaling Calcium ions are important for cellular signalling, as once they enter the cytosol of the cytoplasm they exert allosteric regulatory effects on many enzymes and proteins. Calcium can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein - coupled receptors. Contents 1 Calcium Concentration Regulation 1.1 Phospholipase C Pathway 2 Calcium as a second messenger 3 See also 4 References 5 Further reading Calcium concentration regulation The resting concentration of Ca in the cytoplasm is normally maintained around 100 nM, variously reported as 20,000 - to 100,000-fold lower than typical extracellular concentration. To maintain this low concentration, Ca is actively pumped from the cytosol to the extracellular space, the endoplasmic reticulum ( ER ), and sometimes into the mitochondria. Certain proteins of the cytoplasm and organelles act as buffers by binding Ca. Signaling occurs when the cell is stimulated to release calcium ions ( Ca ) from intracellular stores, and / or when calcium enters the cell through plasma membrane ion channels. Phospholipase C pathway Phospholipase C cleaving PIP2 into IP3 and DAG Specific signals can trigger a sudden increase in the cytoplasmic Ca level up to 500 -- 1,000 nM by opening channels in the endoplasmic reticulum or the plasma membrane. The most common signaling pathway that increases cytoplasmic calcium concentration is the phospholipase C pathway. Many cell surface receptors, including G protein - coupled receptors and receptor tyrosine kinases activate the phospholipase C ( PLC ) enzyme. PLC hydrolyses the membrane phospholipid PIP2 to form IP3 and diacylglycerol ( DAG ), two classical second messengers. DAG recruits protein kinase C ( PKC ), attaching it to the plasma membrane IP diffuses to the endoplasmic reticulum, and binds to an IP3 receptor, The IP3 receptor serves as a Ca channel, and releases Ca from the endoplasmic reticulum. The Ca ions bind to PKC, activating it. Depletion of calcium from the endoplasmic reticulum will lead to Ca entry from outside the cell by activation of `` Store - Operated Channels '' ( SOCs ). This inflowing calcium current that results after stored calcium reserves have been released is referred to as Ca - release - activated Ca current ( ICRAC ). The mechanisms through which ICRAC occurs are currently still under investigation, although two candidate molecules, Orai1 and STIM1, have been linked by several studies, and a model of store - operated calcium influx, involving these molecules, has been proposed. Recent studies have cited the phospholipase A2 beta, nicotinic acid adenine dinucleotide phosphate ( NAADP ), and the protein STIM 1 as possible mediators of ICRAC. Movement of calcium ions from the extracellular compartment to the intracellular compartment alters membrane potential. This is seen in the heart, during the plateau phase of ventricular contraction. In this example, calcium acts to maintain depolarization of the heart. Calcium signaling through ion channels is also important in neuronal synaptic transmission. Calcium as a second messenger Calcium ( as Ca ) is a ubiquitous second messenger with wide - ranging physiological roles. These include muscle contraction, neuronal transmission as in an excitatory synapse, cellular motility ( including the movement of flagella and cilia ), fertilisation, cell growth or proliferation, neurogenesis, learning and memory as with synaptic plasticity, and secretion of saliva. High levels of cytoplasmic calcium can also cause the cell to undergo apoptosis. Other biochemical roles of calcium include regulating enzyme activity, permeability of ion channels, activity of ion pumps, and components of the cytoskeleton. Many of Ca - mediated events occur when the released Ca binds to and activates the regulatory protein calmodulin. Calmodulin may activate calcium - calmodulin - dependent protein kinases, or may act directly on other effector proteins. Besides calmodulin, there are many other Ca - binding proteins that mediate the biological effects of Ca. In neurons, concomitant increases in cytosolic and mitochondrial calcium are important for the synchronization of neuronal electrical activity with mitochondrial energy metabolism. Mitochondrial matrix calcium levels can reach the tens of micromolar levels, which is necessary for the activation of isocitrate dehydrogenase, one of the key regulatory enzymes of the Krebs cycle. In the neuron, the ER may serve in a network integrating numerous extracellular and intracellular signals in a binary membrane system with the plasma membrane. Such an association with the plasma membrane creates the relatively new perception of the ER and theme of `` a neuron within a neuron. '' The ER 's structural characteristics, ability to act as a Ca sink, and specific Ca releasing proteins, serve to create a system that may produce regenerative waves of Ca release that may communicate both locally and globally in the cell. These Ca signals, integrating extracellular and intracellular fluxes, have been implicated to play roles in synaptic plasticity and memory, neurotransmitter release, neuronal excitability and long term changes at the gene transcription level. ER stress is also related to Ca signaling and along with the unfolded protein response, can cause ER associated degradation ( ERAD ) and autophagy. See also Nanodomain European Calcium Society References ^ Jump up to : Clapham, D.E. ( 2007 ). `` Calcium Signaling ''. Cell. 131 ( 6 ) : 1047 -- 1058. doi : 10.1016 / j. cell. 2007.11. 028. PMID 18083096. ^ Jump up to : Demaurex N, Nunes P ( 1 April 2016 ). `` The role of STIM and ORAI proteins in phagocytic immune cells ''. American Journal of Physiology. Cell Physiology. 310 ( 7 ) : C496 -- C508. doi : 10.1152 / ajpcell. 00360.2015. PMC 4824159. PMID 26764049. Jump up ^ Alberts ; Bray ; Hopkin ; Johnson ; Raff ; Lewis ; Roberts ; Walter ( 2014 ). Essential Cell Biology ( 4th ed. ). New York, NY : Garland Science. pp. 548 -- 549. ISBN 978 - 0 - 8153 - 4454 - 4. Jump up ^ Putney, James W. ; Tomita, Takuro ( 2017 - 05 - 15 ). `` Phospholipase C Signaling and Calcium Influx ''. Advances in biological regulation. 52 ( 1 ) : 152 -- 164. doi : 10.1016 / j. advenzreg. 2011.09. 005. ISSN 2212 - 4926. PMC 3560308. PMID 21933679. Jump up ^ Csutora, P. ; et al. ( 2006 ). `` Activation Mechanism for CRAC Current and Store - operated Ca Entry ''. Journal of Biological Chemistry. 281 ( 46 ) : 34926 -- 34935. doi : 10.1074 / jbc. M606504200. PMID 17003039. Jump up ^ Moccia, F. ; et al. ( 2003 ). `` NAADP activates a Ca current that is dependent on F - actin cytoskeleton ''. The FASEB Journal. 17 ( 13 ) : 1907 -- 1909. doi : 10.1096 / fj. 03 - 0178fje. PMID 12923070. Jump up ^ Baba, Y. ; et al. ( 2006 ). `` Coupling of STIM1 to store - operated Ca entry through its constitutive and inducible movement in the endoplasmic reticulum ''. PNAS. 103 ( 45 ) : 16704 -- 16709. doi : 10.1073 / pnas. 0608358103. PMC 1636519. PMID 17075073. Jump up ^ Rash, BG ; Ackman, JB ; Rakic, P ( 26 February 2016 ). `` Bidirectional radial Ca ( 2 + ) activity regulates neurogenesis and migration during early cortical column formation ''. Science Advances. 2 ( 2 ) : e1501733. doi : 10.1126 / sciadv. 1501733. PMC 4771444. PMID 26933693. Jump up ^ Berridge, Michael J. ; Lipp, Peter ; Bootman, Martin D. ( October 2000 ). `` The versatility and universality of calcium signalling ''. Nature Reviews Molecular Cell Biology. 1 ( 1 ) : 11 -- 21. doi : 10.1038 / 35036035. PMID 11413485. Jump up ^ Joseph, Suresh K. ; Hajnóczky, György ( 2007 - 02 - 06 ). `` IP3 receptors in cell survival and apoptosis : Ca2+ release and beyond ''. Apoptosis. 12 ( 5 ) : 951 -- 968. doi : 10.1007 / s10495 - 007 - 0719 - 7. ISSN 1360 - 8185. Jump up ^ Ali ES, Hua J, Wilson CH, Tallis GA, Zhou FH, Rychkov GY, Barritt GJ ( 2016 ). `` The glucagon - like peptide - 1 analogue exendin - 4 reverses impaired intracellular Ca2+ signalling in steatotic hepatocytes ''. BBA − Molecular Cell Research. 1863 : 2135 -- 2146. doi : 10.1016 / j. bbamcr. 2016.05. 006. PMID 27178543. Jump up ^ Koolman, Jan ; Röhm, Klaus - Heinrich ( 2005 ). Color Atlas of Biochemistry. New York : Thieme. ISBN 1 - 58890 - 247 - 1. Jump up ^ Berg, Jeremy ; Tymoczko, John L. ; Gatto, Gregory J. ; Stryer, Lubert ( 2015 ). Biochemistry ( Eighth ed. ). New York, NY : W.H. Freeman and Company. p. 407. ISBN 978 - 1 - 4641 - 2610 - 9. Jump up ^ Ivannikov, M. ; et al. ( 2013 ). `` Mitochondrial Free Ca Levels and Their Effects on Energy Metabolism in Drosophila Motor Nerve Terminals ''. Biophys. J. 104 ( 11 ) : 2353 -- 2361. doi : 10.1016 / j. bpj. 2013.03. 064. PMC 3672877. PMID 23746507. Jump up ^ Ivannikov, M. ; et al. ( 2013 ). `` Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume ''. J. Mol. Neurosci. 49 ( 1 ) : 223 -- 230. doi : 10.1007 / s12031 - 012 - 9848 - 8. PMC 3488359. PMID 22772899. Jump up ^ Berridge, M. ( 1998 ). `` Neuronal calcium signaling ''. Neuron. 21 ( 1 ) : 13 -- 26. doi : 10.1016 / S0896 - 6273 ( 00 ) 80510 - 3. PMID 9697848. Further reading Petersen, Ole H ( 2005 ). `` Ca signalling and Ca - activated ion channels in exocrine acinar cells ''. Cell Calcium. 38 ( 3 -- 4 ) : 171 -- 200. doi : 10.1016 / j. ceca. 2005.06. 024. PMID 16107275. Wikimedia Commons has media related to Calcium signaling. Cell signaling / Signal transduction Signaling pathways GPCR Wnt RTK TGF beta MAPK / ERK Notch JAK - STAT Akt / PKB Fas apoptosis Hippo PI3K / AKT / mTOR pathway Integrin receptors Agents Receptor ligands Hormones Neurotransmitters / Neuropeptides / Neurohormones Cytokines Growth factors Signaling molecules Receptors Cell surface Intracellular Co-receptor Second messenger cAMP - dependent pathway Ca signaling Lipid signaling Assistants : Signal transducing adaptor protein Scaffold protein Transcription factors General Transcription preinitiation complex TFIID TFIIH By distance Juxtacrine Autocrine / Paracrine Endocrine Other concepts Intracrine action Neurocrine signaling Synaptic transmission Chemical synapse Neuroendocrine signaling Exocrine signalling Pheromones Mechanotransduction Phototransduction Ion channel gating Gap junction Cell signaling : calcium signaling and calcium metabolism Cell membrane Ion pumps SERCA Sodium - calcium exchanger Cell membrane calcium channels VDCC TRP NMDA receptor AMPA receptor 5 - HT3 receptor P2X purinoreceptor Adhesion molecules Cadherin Other Calcium - sensing receptor Intracellular signaling & calc. regulation Second messengers IP3 NAADP cADPR Store gates ( ligand - gated calcium channel ) IP3 receptor CICR Ryanodine receptor Molecular switches, and kinases Troponin C Calmodulin CaM kinases PKC NCS Chelators and calcium sensors Calbindin S100 pervalbumin Calretinin Calsequestrin Sarcalumenin Phospholamban Synaptotagmins Proteases Calpain Cytoskeleton remodeling proteins Gelsolin Chaperones Calreticulin Calnexin Other Vitamin D Calcium - binding protein domains EF hand domain C2 domain Extracellular ligands Parathyroid hormone Calcitonin Calcium - binding proteins Intracellular calcium - sensing proteins Calmodulin Calnexin Calreticulin Gelsolin neuronal Hippocalcin Neurocalcin Recoverin Membrane protein Annexin A1 A2 A5 Fibulin FBLN1 FBLN2 FBLN5 Vitamin D - dependent calcium - binding protein / Calbindin Calexcitin Calsequestrin Osteocalcin Osteonectin S - 100 Synaptotagmin Cytoskeleton Troponin C Extracellular matrix Matrix gla protein Retrieved from `` https://en.wikipedia.org/w/index.php?title=Calcium_signaling&oldid=811975906 '' Categories : Cell signaling Signal transduction Talk Contents About Wikipedia 日本 語 Українська Edit links This page was last edited on 25 November 2017, at 04 : 31. 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Question: which second messenger molecule acts on the endoplasmic reticulum to release calcium ions
Answer: Calcium ions