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 DRUG D00110 Cocaine (USP) D00197 Reserpine (JP18/USP/INN) D00228 Amoxapine (JP18/USP/INN) D00367 Mazindol (JAN/USP/INN) D00394 Trimipramine (USAN/INN) D00484 Protriptyline hydrochloride (USP) D00783 Botulinum toxin type A (JAN) D00809 Amitriptyline hydrochloride (JP18/USP) D00811 Clomipramine hydrochloride (JP18/USP) D00812 Desipramine hydrochloride (JAN/USP) D00814 Doxepin hydrochloride (USP) D00815 Imipramine hydrochloride (JP18/USP) D00816 Nortriptyline hydrochloride (JP18/USP/INN) D00817 Bupropion hydrochloride (JAN/USP) D00818 Maprotiline hydrochloride (JP18/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 (JP18/USP) D02237 Guanethidine sulfate (USAN) D02242 Methamphetamine hydrochloride (JP18/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) D10186 Bitopertin (JAN/USAN/INN) D10199 Tapentadol hydrochloride (JAN) D10443 Liafensine (USAN/INN) D10675 Valbenazine (USAN/INN) D10697 Centanafadine (USAN/INN) D10698 Centanafadine hydrochloride (USAN) D10700 Dasotraline (USAN/INN) D10701 Deutetrabenazine (USAN/INN) D10870 Dasotraline hydrochloride (USAN) D10921 Daxibotulinumtoxin A (USAN) D10949 Letibotulinumtoxin A (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) D11940 Toludesvenlafaxine (USAN/INN) D11941 Toludesvenlafaxine hydrochloride (USAN) D12403 Venlafaxine besylate monohydrate D12527 Iclepertin (JAN/USAN/INN) D12715 Tenamfetamine (INN) D12716 Mesocarb (INN) D12937 Midomafetamine hydrochloride (USAN) DBLINKS GO: 0016079 0048488 ORGANISM Homo sapiens (human) [GN:hsa] GENE 101927180 ATP6V1FP2; V-type proton ATPase subunit F-like [KO:K02151] 10312 TCIRG1; T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 [KO:K02154] 10497 UNC13B; unc-13 homolog B [KO:K15293] 10814 CPLX2; complexin 2 [KO:K15294] 10815 CPLX1; complexin 1 [KO:K15294] 112755 STX1B; syntaxin 1B [KO:K08486] 1173 AP2M1; adaptor related protein complex 2 subunit mu 1 [KO:K11826] 1175 AP2S1; adaptor related protein complex 2 subunit sigma 1 [KO:K11827] 1211 CLTA; clathrin light chain A [KO:K04644] 1212 CLTB; clathrin light chain B [KO:K04645] 1213 CLTC; clathrin heavy chain [KO:K04646] 127124 ATP6V1G3; ATPase H+ transporting V1 subunit G3 [KO:K02152] 140679 SLC32A1; solute carrier family 32 member 1 [KO:K15015] 155066 ATP6V0E2; ATPase H+ transporting V0 subunit e2 [KO:K02153] 160 AP2A1; adaptor related protein complex 2 subunit alpha 1 [KO:K11824] 161 AP2A2; adaptor related protein complex 2 subunit alpha 2 [KO:K11824] 163 AP2B1; adaptor related protein complex 2 subunit beta 1 [KO:K11825] 1759 DNM1; dynamin 1 [KO:K01528] [EC:3.6.5.5] 1785 DNM2; dynamin 2 [KO:K23484] 2054 STX2; syntaxin 2 [KO:K08486] 22999 RIMS1; regulating synaptic membrane exocytosis 1 [KO:K15291] 23025 UNC13A; unc-13 homolog A [KO:K15293] 23545 ATP6V0A2; ATPase H+ transporting V0 subunit a2 [KO:K02154] 245972 ATP6V0D2; ATPase H+ transporting V0 subunit d2 [KO:K02146] 245973 ATP6V1C2; ATPase H+ transporting V1 subunit C2 [KO:K02148] 246213 SLC17A8; solute carrier family 17 member 8 [KO:K12302] 26052 DNM3; dynamin 3 [KO:K01528] [EC:3.6.5.5] 339302 CPLX4; complexin 4 [KO:K15295] 440279 UNC13C; unc-13 homolog C [KO:K15293] 4905 NSF; N-ethylmaleimide sensitive factor, vesicle fusing ATPase [KO:K06027] [EC:3.6.4.6] 50617 ATP6V0A4; ATPase H+ transporting V0 subunit a4 [KO:K02154] 51382 ATP6V1D; ATPase H+ transporting V1 subunit D [KO:K02149] 51606 ATP6V1H; ATPase H+ transporting V1 subunit H [KO:K02144] 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] 527 ATP6V0C; ATPase H+ transporting V0 subunit c [KO:K02155] 528 ATP6V1C1; ATPase H+ transporting V1 subunit C1 [KO:K02148] 529 ATP6V1E1; ATPase H+ transporting V1 subunit E1 [KO:K02150] 533 ATP6V0B; ATPase H+ transporting V0 subunit b [KO:K03661] 534 ATP6V1G2; ATPase H+ transporting V1 subunit G2 [KO:K02152] 535 ATP6V0A1; ATPase H+ transporting V0 subunit a1 [KO:K02154] 57030 SLC17A7; solute carrier family 17 member 7 [KO:K12302] 57084 SLC17A6; solute carrier family 17 member 6 [KO:K12302] 5864 RAB3A; RAB3A, member RAS oncogene family [KO:K07882] 594855 CPLX3; complexin 3 [KO:K15295] 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] 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] 6534 SLC6A7; solute carrier family 6 member 7 [KO:K05040] 6536 SLC6A9; solute carrier family 6 member 9 [KO:K05038] 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] 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] 6616 SNAP25; synaptosome associated protein 25 [KO:K18211] 6804 STX1A; syntaxin 1A [KO:K04560] 6809 STX3; syntaxin 3 [KO:K08486] 6812 STXBP1; syntaxin binding protein 1 [KO:K15292] 6844 VAMP2; vesicle associated membrane protein 2 [KO:K13504] 6857 SYT1; synaptotagmin 1 [KO:K15290] 773 CACNA1A; calcium voltage-gated channel subunit alpha1 A [KO:K04344] 774 CACNA1B; calcium voltage-gated channel subunit alpha1 B [KO:K04849] 8218 CLTCL1; clathrin heavy chain like 1 [KO:K04646] 8775 NAPA; NSF attachment protein alpha [KO:K15296] 8992 ATP6V0E1; ATPase H+ transporting V0 subunit e1 [KO:K02153] 90423 ATP6V1E2; ATPase H+ transporting V1 subunit E2 [KO:K02150] 9114 ATP6V0D1; ATPase H+ transporting V0 subunit d1 [KO:K02146] 9152 SLC6A5; solute carrier family 6 member 5 [KO:K05038] 9296 ATP6V1F; ATPase H+ transporting V1 subunit F [KO:K02151] 9550 ATP6V1G1; ATPase H+ transporting V1 subunit G1 [KO:K02152] 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 PMID:12827282 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 PMID:18275379 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 PMID:10212473 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 PMID:20634814 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 PMID:17767192 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 PMID:15217342 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 PMID:12563290 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 PMID:16990140 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 PMID:12094216 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 PMID:12154365 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 PMID:18726177 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 REL_PATHWAY hsa04144 Endocytosis hsa04724 Glutamatergic synapse hsa04725 Cholinergic synapse hsa04726 Serotonergic synapse hsa04727 GABAergic synapse hsa04728 Dopaminergic synapse KO_PATHWAY ko04721 ///