KEGG PATHWAY: hsa04721

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

Disease

H00606	Early infantile epileptic encephalopathy
H00700	Centronuclear myopathy
H00749	Episodic ataxias
H00775	Familial or sporadic hemiplegic migraine

Drug

D00197	Reserpine (JP16/USP/INN)
D06363	Ziconotide (USAN/INN)
D08575	Tetrabenazine (JAN/INN)
D08686	Ziconotide acetate
D10012	Incobotulinumtoxin A (USAN)

Other DBs

BSID:

373900

GO:

0016079 0048488

Organism

Homo sapiens (human) [GN:hsa]

Gene

140679	SLC32A1; solute carrier family 32 (GABA vesicular transporter), member 1 [KO:K15015]
6570	SLC18A1; solute carrier family 18 (vesicular monoamine), member 1 [KO:K08155]
6571	SLC18A2; solute carrier family 18 (vesicular monoamine), member 2 [KO:K08155]
6572	SLC18A3; solute carrier family 18 (vesicular acetylcholine), member 3 [KO:K14636]
57084	SLC17A6; solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6 [KO:K12302]
246213	SLC17A8; solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 8 [KO:K12302]
57030	SLC17A7; solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 7 [KO:K12302]
6857	SYT1; synaptotagmin I [KO:K15290]
6844	VAMP2; vesicle-associated membrane protein 2 (synaptobrevin 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 (brain) [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 (C. elegans) [KO:K15293]
10497	UNC13B; unc-13 homolog B (C. elegans) [KO:K15293]
440279	UNC13C; unc-13 homolog C (C. elegans) [KO:K15293]
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 channel, voltage-dependent, P/Q type, alpha 1A subunit [KO:K04344]
774	CACNA1B; calcium channel, voltage-dependent, N type, alpha 1B subunit [KO:K04849]
4905	NSF; N-ethylmaleimide-sensitive factor [KO:K06027] [EC:3.6.4.6]
8775	NAPA; N-ethylmaleimide-sensitive factor attachment protein, alpha [KO:K15296]
1759	DNM1; dynamin 1 [KO:K01528] [EC:3.6.5.5]
1785	DNM2; dynamin 2 [KO:K01528] [EC:3.6.5.5]
10059	DNM1L; dynamin 1-like [KO:K01528] [EC:3.6.5.5]
26052	DNM3; dynamin 3 [KO:K01528] [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 (Hc) [KO:K04646]
8218	CLTCL1; clathrin, heavy chain-like 1 [KO:K04646]
161	AP2A2; adaptor-related protein complex 2, alpha 2 subunit [KO:K11824]
160	AP2A1; adaptor-related protein complex 2, alpha 1 subunit [KO:K11824]
163	AP2B1; adaptor-related protein complex 2, beta 1 subunit [KO:K11825]
1173	AP2M1; adaptor-related protein complex 2, mu 1 subunit [KO:K11826]
1175	AP2S1; adaptor-related protein complex 2, sigma 1 subunit [KO:K11827]
523	ATP6V1A; ATPase, H+ transporting, lysosomal 70kDa, V1 subunit A [KO:K02145] [EC:3.6.3.14]
525	ATP6V1B1; ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B1 [KO:K02147] [EC:3.6.3.14]
526	ATP6V1B2; ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B2 [KO:K02147] [EC:3.6.3.14]
245973	ATP6V1C2; ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C2 [KO:K02148] [EC:3.6.3.14]
528	ATP6V1C1; ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C1 [KO:K02148] [EC:3.6.3.14]
51382	ATP6V1D; ATPase, H+ transporting, lysosomal 34kDa, V1 subunit D [KO:K02149] [EC:3.6.3.14]
90423	ATP6V1E2; ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E2 [KO:K02150] [EC:3.6.3.14]
529	ATP6V1E1; ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E1 [KO:K02150] [EC:3.6.3.14]
9296	ATP6V1F; ATPase, H+ transporting, lysosomal 14kDa, V1 subunit F [KO:K02151] [EC:3.6.3.14]
9550	ATP6V1G1; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G1 [KO:K02152] [EC:3.6.3.14]
127124	ATP6V1G3; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G3 [KO:K02152] [EC:3.6.3.14]
534	ATP6V1G2; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2 [KO:K02152] [EC:3.6.3.14]
8992	ATP6V0E1; ATPase, H+ transporting, lysosomal 9kDa, V0 subunit e1 [KO:K02153] [EC:3.6.3.14]
155066	ATP6V0E2; ATPase, H+ transporting V0 subunit e2 [KO:K02153] [EC:3.6.3.14]
10312	TCIRG1; T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 subunit A3 [KO:K02154] [EC:3.6.3.14]
23545	ATP6V0A2; ATPase, H+ transporting, lysosomal V0 subunit a2 [KO:K02154] [EC:3.6.3.14]
50617	ATP6V0A4; ATPase, H+ transporting, lysosomal V0 subunit a4 [KO:K02154] [EC:3.6.3.14]
535	ATP6V0A1; ATPase, H+ transporting, lysosomal V0 subunit a1 [KO:K02154] [EC:3.6.3.14]
9114	ATP6V0D1; ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d1 [KO:K02146] [EC:3.6.3.14]
245972	ATP6V0D2; ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d2 [KO:K02146] [EC:3.6.3.14]
51606	ATP6V1H; ATPase, H+ transporting, lysosomal 50/57kDa, V1 subunit H [KO:K02144] [EC:3.6.3.14]
527	ATP6V0C; ATPase, H+ transporting, lysosomal 16kDa, V0 subunit c [KO:K02155] [EC:3.6.3.14]
533	ATP6V0B; ATPase, H+ transporting, lysosomal 21kDa, V0 subunit b [KO:K03661] [EC:3.6.3.14]
6616	SNAP25; synaptosomal-associated protein, 25kDa [KO:K08508]

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)

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)

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)

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)

Reference

PMID:17767192

Authors

Carr CM, Munson M

Title

Tag team action at the synapse.

Journal

EMBO Rep 8:834-8 (2007)

Reference

PMID:15217342

Authors

Sudhof TC

Title

The synaptic vesicle cycle.

Journal

Annu Rev Neurosci 27:509-47 (2004)

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)

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)

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)

Reference

PMID:7791897

Authors

Sudhof TC

Title

The synaptic vesicle cycle: a cascade of protein-protein interactions.

Journal

Nature 375:645-53 (1995)

Reference

PMID:12154365

Authors

Rizo J, Sudhof TC

Title

Snares and Munc18 in synaptic vesicle fusion.

Journal

Nat Rev Neurosci 3:641-53 (2002)

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)

KO pathway

ko04721

All links

Ontology (1)   
   KEGG BRITE (1)   
Pathway (1)   
   BioSystems (1)   
Disease (4)   
   KEGG DISEASE (4)   
Drug (5)   
   KEGG DRUG (5)   
Genome (1)   
   KEGG GENOME (1)   
Gene (64)   
   KEGG GENES (64)   
All databases (76)   

Download RDF

DBGET integrated database retrieval system