Neurotransmitter release cycle (WP3192)

Bos taurus

Neurotransmitter is stored in the synaptic vesicle in the pre-synaptic terminal prior to its release in the synaptic cleft upon depolarization of the pre-synaptic membrane. The release of the neurotransmitter is a multi-step process that is controlled by electrical signals passing through the axons in form of action potential. Neurotransmitters include glutamate, acetylcholine, nor-epinephrine, dopamine and seratonin. Each of the neurotransmitter cycle is independently described.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=112310

Authors

Martina Summer-Kutmon , Elisa Cirillo , and Eric Weitz

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

signaling pathway signaling pathway pertinent to the brain and nervous system

Participants

Label Type Compact URI Comment
H+ Metabolite chebi:15378
ATP Metabolite chebi:15422
ADP Metabolite chebi:16761
Pi Metabolite chebi:18367
DA Metabolite chebi:18243
NAd[clathrin-sculptedglutamate transportvesicle lumen] Metabolite chebi:18357
NAd Metabolite chebi:18357
O2 Metabolite chebi:15379
H2O Metabolite chebi:15377
NH3 Metabolite chebi:16134
H2O2 Metabolite chebi:16240
3-Methoxy-4-hydroxyphenylglycol Metabolite chebi:16436
FAD [mitochondrialouter membrane] Metabolite chebi:16238
5HT Metabolite chebi:28790
5HT[clathrin-sculptedmonoamine transportvesicle lumen] Metabolite chebi:28790
DA[clathrin-sculptedmonoamine transportvesicle lumen] Metabolite chebi:18243
Na+ Metabolite chebi:29101
L-Gln Metabolite chebi:18050
NH4+ Metabolite chebi:28938
Glu Metabolite chebi:16015
L-Glu Metabolite chebi:16015
Glu[clathrin-sculptedglutamate transportvesicle lumen] Metabolite chebi:16015
Cho Metabolite chebi:15354
Ac-CoA Metabolite chebi:15351
AcCho Metabolite chebi:15355
CoA-SH Metabolite chebi:15346
O-acetylcholine[clathrin-sculptedacetylcholinetransport vesiclelumen] Metabolite chebi:15355
SLC18A2 Protein ensembl:ENSBTAG00000004739 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q05940
RIMS1 Protein ensembl:ENSBTAG00000020238 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q86UR5
RAB3A Protein ensembl:ENSBTAG00000010635 Rab3A, located in the synaptic vesicle membrane, interacts with RIM ( Rab3A interacting Molecule) and with Doc2. These interactions are beleived to initiate the process of priming which precedes the fuison of the synaptic vesicle with the plasma membrane.
HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P20336
SYT1 Protein ensembl:ENSBTAG00000034693 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P21579
VAMP2 Protein ensembl:ENSBTAG00000003891 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P63027
SNAP25 Protein ensembl:ENSBTAG00000008323 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P60880
STX1A Protein ensembl:ENSBTAG00000017075 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q16623
MAOA Protein ensembl:ENSBTAG00000016206 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P21397
SLC22A2 Protein ensembl:ENSBTAG00000009583 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O15244
SLC38A2 Protein ensembl:ENSBTAG00000011105 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q96QD8
SLC17A7 Protein ensembl:ENSBTAG00000007036 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9P2U7
UNC13B Protein ensembl:ENSBTAG00000011397 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O14795
CHAT Protein ensembl:ENSBTAG00000016814 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P28329
SLC18A3 Protein ensembl:ENSBTAG00000014990 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q16572
SLC5A7 Protein ensembl:ENSBTAG00000004352 HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9GZV3

References

  1. Human choline acetyltransferase (CHAT): partial gene sequence and potential control regions. Toussaint JL, Geoffroy V, Schmitt M, Werner A, Garnier JM, Simoni P, et al. Genomics. 1992 Feb;12(2):412–6. PubMed Europe PMC Scholia
  2. Purification of phosphate-dependent glutaminase from isolated mitochondria of Ehrlich ascites-tumour cells. Quesada AR, Sanchez-Jimenez F, Perez-Rodriguez J, Marquez J, Medina MA, Nuñez de Castro I. Biochem J. 1988 Nov 1;255(3):1031–5. PubMed Europe PMC Scholia
  3. Determination of delta pH in cholinergic synaptic vesicles: its effect on storage and release of acetylcholine. Michaelson DM, Angel I. Life Sci. 1980 Jul 7;27(1):39–44. PubMed Europe PMC Scholia
  4. Functional identification of a vesicular acetylcholine transporter and its expression from a “cholinergic” gene locus. Erickson JD, Varoqui H, Schäfer MK, Modi W, Diebler MF, Weihe E, et al. J Biol Chem. 1994 Sep 2;269(35):21929–32. PubMed Europe PMC Scholia
  5. A human synaptic vesicle monoamine transporter cDNA predicts posttranslational modifications, reveals chromosome 10 gene localization and identifies TaqI RFLPs. Surratt CK, Persico AM, Yang XD, Edgar SR, Bird GS, Hawkins AL, et al. FEBS Lett. 1993 Mar 8;318(3):325–30. PubMed Europe PMC Scholia
  6. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA. Science. 1993 Oct 22;262(5133):578–80. PubMed Europe PMC Scholia
  7. Cloning and characterization of two human polyspecific organic cation transporters. Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, et al. DNA Cell Biol. 1997 Jul;16(7):871–81. PubMed Europe PMC Scholia
  8. Interaction of Munc-18-2 with syntaxin 3 controls the association of apical SNAREs in epithelial cells. Riento K, Galli T, Jansson S, Ehnholm C, Lehtonen E, Olkkonen VM. J Cell Sci. 1998 Sep;111 ( Pt 17):2681–8. PubMed Europe PMC Scholia
  9. Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Augustin I, Rosenmund C, Südhof TC, Brose N. Nature. 1999 Jul 29;400(6743):457–61. PubMed Europe PMC Scholia
  10. Molecular cloning, sequencing and expression studies of the human breast cancer cell glutaminase. Gómez-Fabre PM, Aledo JC, Del Castillo-Olivares A, Alonso FJ, Núñez De Castro I, Campos JA, et al. Biochem J. 2000 Jan 15;345 Pt 2(Pt 2):365–75. PubMed Europe PMC Scholia
  11. Immunoisolation of GABA-specific synaptic vesicles defines a functionally distinct subset of synaptic vesicles. Takamori S, Riedel D, Jahn R. J Neurosci. 2000 Jul 1;20(13):4904–11. PubMed Europe PMC Scholia
  12. Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons. Takamori S, Rhee JS, Rosenmund C, Jahn R. Nature. 2000 Sep 14;407(6801):189–94. PubMed Europe PMC Scholia
  13. Modulation of amyloid precursor protein metabolism by X11alpha /Mint-1. A deletion analysis of protein-protein interaction domains. Mueller HT, Borg JP, Margolis B, Turner RS. J Biol Chem. 2000 Dec 15;275(50):39302–6. PubMed Europe PMC Scholia
  14. Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing. Elgadi KM, Meguid RA, Qian M, Souba WW, Abcouwer SF. Physiol Genomics. 1999 Aug 31;1(2):51–62. PubMed Europe PMC Scholia
  15. Functional characterization of the human high-affinity choline transporter. Okuda T, Haga T. FEBS Lett. 2000 Nov 3;484(2):92–7. PubMed Europe PMC Scholia
  16. Rab3a binding and secretion-enhancing domains in Rim1 are separate and unique. Studies in adrenal chromaffin cells. Sun L, Bittner MA, Holz RW. J Biol Chem. 2001 Apr 20;276(16):12911–7. PubMed Europe PMC Scholia
  17. Glutamine uptake by neurons: interaction of protons with system a transporters. Chaudhry FA, Schmitz D, Reimer RJ, Larsson P, Gray AT, Nicoll R, et al. J Neurosci. 2002 Jan 1;22(1):62–72. PubMed Europe PMC Scholia
  18. Phosphorylation of Munc18 by protein kinase C regulates the kinetics of exocytosis. Barclay JW, Craig TJ, Fisher RJ, Ciufo LF, Evans GJO, Morgan A, et al. J Biol Chem. 2003 Mar 21;278(12):10538–45. PubMed Europe PMC Scholia
  19. Rim, a component of the presynaptic active zone and modulator of exocytosis, binds 14-3-3 through its N terminus. Sun L, Bittner MA, Holz RW. J Biol Chem. 2003 Oct 3;278(40):38301–9. PubMed Europe PMC Scholia
  20. The synaptic vesicle cycle. Sudhof TC. Annu Rev Neurosci. 2004;27:509–47. PubMed Europe PMC Scholia
  21. Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation. Toonen RFG, de Vries KJ, Zalm R, Südhof TC, Verhage M. J Neurochem. 2005 Jun;93(6):1393–400. PubMed Europe PMC Scholia
  22. Expression of GFP-tagged neuronal glutamate transporters in cerebellar Purkinje neurons. Meera P, Dodson PD, Karakossian MH, Otis TS. Neuropharmacology. 2005 Nov;49(6):883–9. PubMed Europe PMC Scholia
  23. Localization of the Na(+)-coupled neutral amino acid transporter 2 in the cerebral cortex. Melone M, Varoqui H, Erickson JD, Conti F. Neuroscience. 2006 Jun 19;140(1):281–92. PubMed Europe PMC Scholia
  24. The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. Bak LK, Schousboe A, Waagepetersen HS. J Neurochem. 2006 Aug;98(3):641–53. PubMed Europe PMC Scholia
  25. Vesicle pools, docking, priming, and release. Becherer U, Rettig J. Cell Tissue Res. 2006 Nov;326(2):393–407. PubMed Europe PMC Scholia
  26. Molecular organization of the presynaptic active zone. Schoch S, Gundelfinger ED. Cell Tissue Res. 2006 Nov;326(2):379–91. PubMed Europe PMC Scholia
  27. Munc18-1 binds directly to the neuronal SNARE complex. Dulubova I, Khvotchev M, Liu S, Huryeva I, Südhof TC, Rizo J. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2697–702. PubMed Europe PMC Scholia
  28. How synaptotagmin promotes membrane fusion. Martens S, Kozlov MM, McMahon HT. Science. 2007 May 25;316(5828):1205–8. PubMed Europe PMC Scholia
  29. Identification of the substrate binding region of vesicular monoamine transporter-2 (VMAT-2) using iodoaminoflisopolol as a novel photoprobe. Gopalakrishnan A, Sievert M, Ruoho AE. Mol Pharmacol. 2007 Dec;72(6):1567–75. PubMed Europe PMC Scholia
  30. The neurotransmitter cycle and quantal size. Edwards RH. Neuron. 2007 Sep 20;55(6):835–58. PubMed Europe PMC Scholia
  31. Synaptotagmin activates membrane fusion through a Ca2+-dependent trans interaction with phospholipids. Stein A, Radhakrishnan A, Riedel D, Fasshauer D, Jahn R. Nat Struct Mol Biol. 2007 Oct;14(10):904–11. PubMed Europe PMC Scholia
  32. Dual modes of Munc18-1/SNARE interactions are coupled by functionally critical binding to syntaxin-1 N terminus. Khvotchev M, Dulubova I, Sun J, Dai H, Rizo J, Südhof TC. J Neurosci. 2007 Nov 7;27(45):12147–55. PubMed Europe PMC Scholia
  33. Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3. Seal RP, Akil O, Yi E, Weber CM, Grant L, Yoo J, et al. Neuron. 2008 Jan 24;57(2):263–75. PubMed Europe PMC Scholia
  34. Syntaxin 1A interaction with the dopamine transporter promotes amphetamine-induced dopamine efflux. Binda F, Dipace C, Bowton E, Robertson SD, Lute BJ, Fog JU, et al. Mol Pharmacol. 2008 Oct;74(4):1101–8. PubMed Europe PMC Scholia
  35. A novel mechanism for GABA synthesis and packaging into synaptic vesicles. Buddhala C, Hsu CC, Wu JY. Neurochem Int. 2009;55(1–3):9–12. PubMed Europe PMC Scholia