KEGG   PATHWAY: hsa04721
Entry
hsa04721                    Pathway                                

Name
Synaptic vesicle cycle - Homo sapiens (human)
Description
Communication between neurons is mediated by the release of neurotransmitter from synaptic vesicles (SVs). At the nerve terminal, SVs cycle through repetitive episodes of exocytosis and endocytosis. SVs are filled with neurotransmitters by active transport. The loaded SVs are then docked at a specialized region of the presynaptic plasma membrane known as the active zone, where they undergo a priming reaction. Upon arrival of an action potential, Ca2+ enters through voltage-gated channels and neurotransmitter is released by exocytosis, usually in less than a millisecond. After fusion, the vesicle is retrieved by endocytosis and reloaded for another round of exocytosis.
Class
Organismal Systems; Nervous system
Pathway map
hsa04721  Synaptic vesicle cycle
hsa04721

Disease
H00700  Centronuclear myopathy
H00749  Episodic ataxias
H00769  Hyperekplexia
H00775  Hemiplegic migraine
H01031  Orthostatic intolerance
H02219  DDOD syndrome
H02419  Glycine encephalopathy with normal serum glycine
Drug
D00110  Cocaine (USP)
D00197  Reserpine (JP17/USP/INN)
D00228  Amoxapine (JP17/USP/INN)
D00367  Mazindol (JAN/USP/INN)
D00394  Trimipramine (USAN/INN)
D00484  Protriptyline hydrochloride (USP)
D00783  Botulinum toxin type A (JAN)
D00809  Amitriptyline hydrochloride (JP17/USP)
D00811  Clomipramine hydrochloride (JP17/USP)
D00812  Desipramine hydrochloride (JAN/USP)
D00814  Doxepin hydrochloride (USP)
D00815  Imipramine hydrochloride (JP17/USP)
D00816  Nortriptyline hydrochloride (JP17/USP/INN)
D00817  Bupropion hydrochloride (JAN/USP)
D00818  Maprotiline hydrochloride (JP17/USP)
D00821  Venlafaxine hydrochloride (JAN/USP)
D01107  Milnacipran hydrochloride (JAN/USAN)
D01179  Duloxetine hydrochloride (JAN/USP)
D01285  Lofepramine hydrochloride (JAN/USAN)
D01296  Methylphenidate hydrochloride (JAN/USP)
D01304  Amezinium metilsulfate (JAN)
D01546  Dothiepin hydrochloride (USAN)
D02074  Amphetamine sulfate (USP)
D02078  Dextroamphetamine sulfate (USP)
D02080  Phendimetrazine tartrate (USP)
D02170  Indeloxazine hydrochloride (JAN/USAN)
D02182  Cocaine hydrochloride (JP17/USP)
D02237  Guanethidine sulfate (USAN)
D02242  Methamphetamine hydrochloride (JP17/USP)
D02408  Trimipramine maleate (JAN/USP)
D02566  Maprotiline (USAN)
D02570  Desvenlafaxine succinate (USAN)
D02571  Sibutramine hydrochloride (USP)
D02572  Viloxazine hydrochloride (USAN)
D02573  Reboxetine mesylate (USAN)
D02574  Atomoxetine hydrochloride (JAN/USP)
D02704  Tampramine fumarate (USAN)
D02735  Rimabotulinumtoxin B (USAN)
D03491  Cidoxepin hydrochloride (USAN)
D03721  Dexmethylphenidate hydrochloride (USAN)
D03740  Dextroamphetamine (USAN)
D03801  Diethylpropion hydrochloride (USP)
D04382  Guanethidine monosulfate (USP)
D04473  Hydroxyamphetamine hydrobromide (USP)
D04747  Lisdexamfetamine dimesylate (USAN)
D04781  Lortalamine (USAN/INN)
D04999  Methylphenidate (USAN/INN)
D05119  Napamezole hydrochloride (USAN)
D05120  Napitane mesylate (USAN)
D05173  Nisoxetine (USAN/INN)
D05200  Nomifensine maleate (USAN)
D05284  Oxaprotiline hydrochloride (USAN)
D05454  Phenmetrazine hydrochloride (USP)
D05458  Phentermine (USAN/INN)
D05459  Phentermine hydrochloride (USP)
D05663  Pyrovalerone hydrochloride (USAN)
D05692  Radafaxine hydrochloride (USAN)
D05997  Talopram hydrochloride (USAN)
D06004  Tandamine hydrochloride (USAN)
D06007  Tapentadol (USAN/INN)
D07334  Imipraminoxide (INN)
D07444  Amfepramone (INN)
D07445  Amfetamine (INN)
D07448  Amitriptyline (INN)
D07449  Amitriptylinoxide (INN)
D07473  Atomoxetine (USP/INN)
D07514  Benzfetamine (INN)
D07515  Benzfetamine hydrochloride
D07591  Bupropion (INN)
D07727  Clomipramine (INN)
D07791  Desipramine (INN)
D07793  Desvenlafaxine (INN)
D07806  Dexmethylphenidate (INN)
D07872  Dosulepin (INN)
D07875  Doxepin (INN)
D07880  Duloxetine (INN)
D07938  Bupropion hydrobromide (USAN)
D08030  Guanethidine (INN)
D08070  Imipramine (INN)
D08071  Imipramine pamoate (USP)
D08072  Imipraminoxide hydrochloride
D08077  Indeloxazine (INN)
D08130  Lisdexamfetamine (INN)
D08140  Lofepramine (INN)
D08187  Metamfetamine (INN)
D08222  Milnacipran (INN)
D08288  Nortriptyline (INN)
D08347  Phendimetrazine (INN)
D08348  Phendimetrazine hydrochloride
D08447  Protriptyline (INN)
D08472  Reboxetine (INN)
D08513  Sibutramine (INN)
D08575  Tetrabenazine (JAN/INN)
D08670  Venlafaxine (INN)
D08673  Viloxazine (INN)
D09340  Esreboxetine (USAN/INN)
D09341  Esreboxetine succinate (USAN)
D10012  Incobotulinumtoxin A (JAN/USAN)
D10072  Levomilnacipran (USAN/INN)
D10088  Amitifadine (USAN)
D10089  Amitifadine hydrochloride (USAN)
D10133  Levomilnacipran hydrochloride (USAN)
D10199  Tapentadol hydrochloride (JAN)
D10443  Liafensine (USAN)
D10675  Valbenazine (USAN/INN)
D10697  Centanafadine (USAN)
D10698  Centanafadine hydrochloride (USAN)
D10700  Dasotraline (USAN/INN)
D10701  Deutetrabenazine (USAN/INN)
D10870  Dasotraline hydrochloride (USAN)
D10999  Valbenazine tosylate (USAN)
D11172  Midomafetamine (USAN/INN)
D11315  Solriamfetol (USAN)
D11328  Solriamfetol hydrochloride (USAN)
D11405  Prabotulinumtoxin A (USAN)
D11619  Desvenlafaxine succinate anhydrous
D11622  Amphetamine aspartate monohydrate
D11623  Dextroamphetamine saccharate
D11688  Ampreloxetine (USAN/INN)
D11689  Ampreloxetine hydrochloride (USAN)
Other DBs
GO: 0016079 0048488
Organism
Homo sapiens (human) [GN:hsa]
Gene
140679  SLC32A1; solute carrier family 32 member 1 [KO:K15015]
6570  SLC18A1; solute carrier family 18 member A1 [KO:K08155]
6571  SLC18A2; solute carrier family 18 member A2 [KO:K08155]
6572  SLC18A3; solute carrier family 18 member A3 [KO:K14636]
57084  SLC17A6; solute carrier family 17 member 6 [KO:K12302]
246213  SLC17A8; solute carrier family 17 member 8 [KO:K12302]
57030  SLC17A7; solute carrier family 17 member 7 [KO:K12302]
6857  SYT1; synaptotagmin 1 [KO:K15290]
6844  VAMP2; vesicle associated membrane protein 2 [KO:K13504]
5864  RAB3A; RAB3A, member RAS oncogene family [KO:K07882]
22999  RIMS1; regulating synaptic membrane exocytosis 1 [KO:K15291]
6804  STX1A; syntaxin 1A [KO:K04560]
2054  STX2; syntaxin 2 [KO:K08486]
6809  STX3; syntaxin 3 [KO:K08486]
112755  STX1B; syntaxin 1B [KO:K08486]
6812  STXBP1; syntaxin binding protein 1 [KO:K15292]
23025  UNC13A; unc-13 homolog A [KO:K15293]
10497  UNC13B; unc-13 homolog B [KO:K15293]
440279  UNC13C; unc-13 homolog C [KO:K15293]
6616  SNAP25; synaptosome associated protein 25 [KO:K18211]
10815  CPLX1; complexin 1 [KO:K15294]
10814  CPLX2; complexin 2 [KO:K15294]
594855  CPLX3; complexin 3 [KO:K15295]
339302  CPLX4; complexin 4 [KO:K15295]
773  CACNA1A; calcium voltage-gated channel subunit alpha1 A [KO:K04344]
774  CACNA1B; calcium voltage-gated channel subunit alpha1 B [KO:K04849]
4905  NSF; N-ethylmaleimide sensitive factor, vesicle fusing ATPase [KO:K06027] [EC:3.6.4.6]
8775  NAPA; NSF attachment protein alpha [KO:K15296]
1759  DNM1; dynamin 1 [KO:K01528] [EC:3.6.5.5]
26052  DNM3; dynamin 3 [KO:K01528] [EC:3.6.5.5]
1785  DNM2; dynamin 2 [KO:K23484] [EC:3.6.5.5]
1211  CLTA; clathrin light chain A [KO:K04644]
1212  CLTB; clathrin light chain B [KO:K04645]
1213  CLTC; clathrin heavy chain [KO:K04646]
8218  CLTCL1; clathrin heavy chain like 1 [KO:K04646]
161  AP2A2; adaptor related protein complex 2 subunit alpha 2 [KO:K11824]
160  AP2A1; adaptor related protein complex 2 subunit alpha 1 [KO:K11824]
163  AP2B1; adaptor related protein complex 2 subunit beta 1 [KO:K11825]
1173  AP2M1; adaptor related protein complex 2 subunit mu 1 [KO:K11826]
1175  AP2S1; adaptor related protein complex 2 subunit sigma 1 [KO:K11827]
523  ATP6V1A; ATPase H+ transporting V1 subunit A [KO:K02145] [EC:7.1.2.2]
525  ATP6V1B1; ATPase H+ transporting V1 subunit B1 [KO:K02147]
526  ATP6V1B2; ATPase H+ transporting V1 subunit B2 [KO:K02147]
245973  ATP6V1C2; ATPase H+ transporting V1 subunit C2 [KO:K02148]
528  ATP6V1C1; ATPase H+ transporting V1 subunit C1 [KO:K02148]
51382  ATP6V1D; ATPase H+ transporting V1 subunit D [KO:K02149]
90423  ATP6V1E2; ATPase H+ transporting V1 subunit E2 [KO:K02150]
529  ATP6V1E1; ATPase H+ transporting V1 subunit E1 [KO:K02150]
9296  ATP6V1F; ATPase H+ transporting V1 subunit F [KO:K02151]
9550  ATP6V1G1; ATPase H+ transporting V1 subunit G1 [KO:K02152]
127124  ATP6V1G3; ATPase H+ transporting V1 subunit G3 [KO:K02152]
534  ATP6V1G2; ATPase H+ transporting V1 subunit G2 [KO:K02152]
8992  ATP6V0E1; ATPase H+ transporting V0 subunit e1 [KO:K02153]
155066  ATP6V0E2; ATPase H+ transporting V0 subunit e2 [KO:K02153]
10312  TCIRG1; T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 [KO:K02154]
23545  ATP6V0A2; ATPase H+ transporting V0 subunit a2 [KO:K02154]
50617  ATP6V0A4; ATPase H+ transporting V0 subunit a4 [KO:K02154]
535  ATP6V0A1; ATPase H+ transporting V0 subunit a1 [KO:K02154]
9114  ATP6V0D1; ATPase H+ transporting V0 subunit d1 [KO:K02146]
245972  ATP6V0D2; ATPase H+ transporting V0 subunit d2 [KO:K02146]
51606  ATP6V1H; ATPase H+ transporting V1 subunit H [KO:K02144]
527  ATP6V0C; ATPase H+ transporting V0 subunit c [KO:K02155]
533  ATP6V0B; ATPase H+ transporting V0 subunit b [KO:K03661]
6529  SLC6A1; solute carrier family 6 member 1 [KO:K05034]
6530  SLC6A2; solute carrier family 6 member 2 [KO:K05035]
6531  SLC6A3; solute carrier family 6 member 3 [KO:K05036]
6532  SLC6A4; solute carrier family 6 member 4 [KO:K05037]
9152  SLC6A5; solute carrier family 6 member 5 [KO:K05038]
6536  SLC6A9; solute carrier family 6 member 9 [KO:K05038]
6534  SLC6A7; solute carrier family 6 member 7 [KO:K05040]
6538  SLC6A11; solute carrier family 6 member 11 [KO:K05044]
6539  SLC6A12; solute carrier family 6 member 12 [KO:K05045]
6540  SLC6A13; solute carrier family 6 member 13 [KO:K05046]
6505  SLC1A1; solute carrier family 1 member 1 [KO:K05612]
6506  SLC1A2; solute carrier family 1 member 2 [KO:K05613]
6507  SLC1A3; solute carrier family 1 member 3 [KO:K05614]
6511  SLC1A6; solute carrier family 1 member 6 [KO:K05617]
6512  SLC1A7; solute carrier family 1 member 7 [KO:K05618]
Compound
C00002  ATP
C00025  L-Glutamate
C00037  Glycine
C00076  Calcium cation
C00080  H+
C00334  4-Aminobutanoate
C00388  Histamine
C00547  L-Noradrenaline
C00780  Serotonin
C01996  Acetylcholine
C03758  Dopamine
C16041  Leu-enkephalin
Reference
  Authors
Li L, Chin LS
  Title
The molecular machinery of synaptic vesicle exocytosis.
  Journal
Cell Mol Life Sci 60:942-60 (2003)
DOI:10.1007/s00018-003-2240-7
Reference
  Authors
Nestler EJ, Hyman SE, Malenka RC.
  Title
Molecular neuropharmacology: A foundation for clinical neuroscience
  Journal
The McGraw-Hill Companies, Inc. (2001)
Reference
  Authors
Chapman ER
  Title
How does synaptotagmin trigger neurotransmitter release?
  Journal
Annu Rev Biochem 77:615-41 (2008)
DOI:10.1146/annurev.biochem.77.062005.101135
Reference
  Authors
Benfenati F, Onofri F, Giovedi S
  Title
Protein-protein interactions and protein modules in the control of neurotransmitter release.
  Journal
Philos Trans R Soc Lond B Biol Sci 354:243-57 (1999)
DOI:10.1098/rstb.1999.0376
Reference
  Authors
de Saint Basile G, Menasche G, Fischer A
  Title
Molecular mechanisms of biogenesis and exocytosis of cytotoxic granules.
  Journal
Nat Rev Immunol 10:568-79 (2010)
DOI:10.1038/nri2803
Reference
  Authors
Carr CM, Munson M
  Title
Tag team action at the synapse.
  Journal
EMBO Rep 8:834-8 (2007)
DOI:10.1038/sj.embor.7401051
Reference
  Authors
Sudhof TC
  Title
The synaptic vesicle cycle.
  Journal
Annu Rev Neurosci 27:509-47 (2004)
DOI:10.1146/annurev.neuro.26.041002.131412
Reference
  Authors
Gundelfinger ED, Kessels MM, Qualmann B
  Title
Temporal and spatial coordination of exocytosis and endocytosis.
  Journal
Nat Rev Mol Cell Biol 4:127-39 (2003)
DOI:10.1038/nrm1016
Reference
  Authors
Tang J, Maximov A, Shin OH, Dai H, Rizo J, Sudhof TC
  Title
A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis.
  Journal
Cell 126:1175-87 (2006)
DOI:10.1016/j.cell.2006.08.030
Reference
  Authors
Chapman ER
  Title
Synaptotagmin: a Ca(2+) sensor that triggers exocytosis?
  Journal
Nat Rev Mol Cell Biol 3:498-508 (2002)
DOI:10.1038/nrm855
Reference
PMID:7791897
  Authors
Sudhof TC
  Title
The synaptic vesicle cycle: a cascade of protein-protein interactions.
  Journal
Nature 375:645-53 (1995)
DOI:10.1038/375645a0
Reference
  Authors
Rizo J, Sudhof TC
  Title
Snares and Munc18 in synaptic vesicle fusion.
  Journal
Nat Rev Neurosci 3:641-53 (2002)
DOI:10.1038/nrn898
Reference
  Authors
Malsam J, Kreye S, Sollner TH
  Title
Membrane fusion: SNAREs and regulation.
  Journal
Cell Mol Life Sci 65:2814-32 (2008)
DOI:10.1007/s00018-008-8352-3
Related
pathway
hsa04144  Endocytosis
hsa04724  Glutamatergic synapse
hsa04725  Cholinergic synapse
hsa04726  Serotonergic synapse
hsa04727  GABAergic synapse
hsa04728  Dopaminergic synapse
KO pathway
ko04721   

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