KEGG   PATHWAY: mcc04725
Entry
mcc04725                    Pathway                                
Name
Cholinergic synapse - Macaca mulatta (rhesus monkey)
Description
Acetylcholine (ACh) is a neurotransmitter widely distributed in the central (and also peripheral, autonomic and enteric) nervous system (CNS). In the CNS, ACh facilitates many functions, such as learning, memory, attention and motor control. When released in the synaptic cleft, ACh binds to two distinct types of receptors: Ionotropic nicotinic acetylcholine receptors (nAChR) and metabotropic muscarinic acetylcholine receptors (mAChRs). The activation of nAChR by ACh leads to the rapid influx of Na+ and Ca2+ and subsequent cellular depolarization. Activation of mAChRs is relatively slow (milliseconds to seconds) and, depending on the subtypes present (M1-M5), they directly alter cellular homeostasis of phospholipase C, inositol trisphosphate, cAMP, and free calcium. In the cleft, ACh may also be hydrolyzed by acetylcholinesterase (AChE) into choline and acetate. The choline derived from ACh hydrolysis is recovered by a presynaptic high-affinity choline transporter (CHT).
Class
Organismal Systems; Nervous system
Pathway map
mcc04725  Cholinergic synapse
mcc04725

Other DBs
GO: 0032222
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
709977  CHAT; choline O-acetyltransferase isoform X1 [KO:K00623] [EC:2.3.1.6]
713370  ACHE; acetylcholinesterase precursor [KO:K01049] [EC:3.1.1.7]
710053  SLC18A3; vesicular acetylcholine transporter [KO:K14636]
574362  CHRM1; muscarinic acetylcholine receptor M1 [KO:K04129]
708901  CHRM3; muscarinic acetylcholine receptor M3 [KO:K04131]
574330  CHRM5; muscarinic acetylcholine receptor M5 [KO:K04133]
705680  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
721649  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
701951  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
718418  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
718387  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
717764  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
703669  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
708714  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
718040  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
718412  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
701195  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
720263  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
721211  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 isoform X1 [KO:K04926]
719614  KCNQ2; potassium voltage-gated channel subfamily KQT member 2 isoform X2 [KO:K04927]
700785  KCNQ3; potassium voltage-gated channel subfamily KQT member 3 [KO:K04928]
100426025  KCNQ4; potassium voltage-gated channel subfamily KQT member 4 [KO:K04929]
715426  KCNQ5; potassium voltage-gated channel subfamily KQT member 5 [KO:K04930]
574189  KCNJ2; inward rectifier potassium channel 2 [KO:K04996]
705326  KCNJ12; ATP-sensitive inward rectifier potassium channel 12 [KO:K05005]
721015  KCNJ4; inward rectifier potassium channel 4 [KO:K04998]
718011  KCNJ14; ATP-sensitive inward rectifier potassium channel 14 [KO:K05007]
714780  CHRM2; muscarinic acetylcholine receptor M2 [KO:K04130]
574195  CHRM4; muscarinic acetylcholine receptor M4 [KO:K04132]
699310  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
703780  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
708940  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
574394  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
703399  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
719248  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
713913  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
709489  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
695441  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
710000  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
100169972  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
718223  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
703336  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
710548  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
711335  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
114673987  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 isoform X1 [KO:K04544]
708193  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
700606  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
100424606  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
114673968  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
722398  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
700724  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
698840  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
696473  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
693675  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
698857  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
722027  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
722023  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
698830  HRAS; GTPase HRas [KO:K02833]
707977  KRAS; GTPase KRas [KO:K07827]
709089  NRAS; GTPase NRas [KO:K07828]
710415  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
708938  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
698569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
702077  FOS; proto-oncogene c-Fos [KO:K04379]
574230  CHRNA7; neuronal acetylcholine receptor subunit alpha-7 precursor [KO:K04809]
719678  neuronal acetylcholine receptor subunit alpha-4 isoform X2 [KO:K04806]
114670571  CHRNA4; LOW QUALITY PROTEIN: neuronal acetylcholine receptor subunit alpha-4 [KO:K04806]
716830  CHRNB2; neuronal acetylcholine receptor subunit beta-2 precursor [KO:K04813]
716571  CHRNA3; neuronal acetylcholine receptor subunit alpha-3 [KO:K04805]
106996685  CHRNB4; neuronal acetylcholine receptor subunit beta-4 [KO:K04815]
705725  CHRNA6; neuronal acetylcholine receptor subunit alpha-6 isoform X1 [KO:K04808]
697230  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
695328  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
693523  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
714684  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
715897  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
707978  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
694730  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
695792  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
706789  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
709728  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
718632  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
700652  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
708717  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
703965  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
714981  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
713391  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
696350  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
721825  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
715951  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
697718  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
705980  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
702504  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
706977  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X11 [KO:K04515] [EC:2.7.11.17]
710540  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
712322  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
694184  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
574214  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
716098  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
709959  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
710552  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
707310  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
719367  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
698996  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
714717  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
697747  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
700591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
707407  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
718291  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X5 [KO:K04344]
721452  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
721721  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X13 [KO:K04850]
693924  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
715787  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
708706  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
714093  SLC5A7; high affinity choline transporter 1 [KO:K14387]
Compound
C00010  CoA
C00024  Acetyl-CoA
C00033  Acetate
C00076  Calcium cation
C00114  Choline
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01996  Acetylcholine
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
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
Nicholls JG, Martin AR, Wallace BG, Fuchs PA.
  Title
From neuron to brain, 4th ed.
  Journal
Sunderland, MA: Sinauer associates (2001)
Reference
PMID:15165747
  Authors
Dajas-Bailador F, Wonnacott S
  Title
Nicotinic acetylcholine receptors and the regulation of neuronal signalling.
  Journal
Trends Pharmacol Sci 25:317-24 (2004)
DOI:10.1016/j.tips.2004.04.006
Reference
PMID:19712465
  Authors
Resende RR, Adhikari A
  Title
Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation.
  Journal
Cell Commun Signal 7:20 (2009)
DOI:10.1186/1478-811X-7-20
Reference
PMID:19378880
  Authors
Origlia N, Kuczewski N, Pesavento E, Aztiria E, Domenici L
  Title
The role of cholinergic system in neuronal plasticity: focus on visual cortex and muscarinic receptors.
  Journal
Arch Ital Biol 146:165-88 (2008)
Reference
PMID:21550798
  Authors
Oldenburg IA, Ding JB
  Title
Cholinergic modulation of synaptic integration and dendritic excitability in the striatum.
  Journal
Curr Opin Neurobiol 21:425-32 (2011)
DOI:10.1016/j.conb.2011.04.004
Reference
PMID:12893537
  Authors
Lanzafame AA, Christopoulos A, Mitchelson F
  Title
Cellular signaling mechanisms for muscarinic acetylcholine receptors.
  Journal
Receptors Channels 9:241-60 (2003)
DOI:10.3109/10606820308263
Reference
PMID:20446119
  Authors
Brown DA
  Title
Muscarinic acetylcholine receptors (mAChRs) in the nervous system: some functions and mechanisms.
  Journal
J Mol Neurosci 41:340-6 (2010)
DOI:10.1007/s12031-010-9377-2
Reference
PMID:11738031
  Authors
Chang KT, Berg DK
  Title
Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons.
  Journal
Neuron 32:855-65 (2001)
DOI:10.1016/S0896-6273(01)00516-5
Reference
PMID:11283752
  Authors
Soreq H, Seidman S
  Title
Acetylcholinesterase--new roles for an old actor.
  Journal
Nat Rev Neurosci 2:294-302 (2001)
DOI:10.1038/35067589
Reference
PMID:12436417
  Authors
Sharma G, Vijayaraghavan S
  Title
Nicotinic receptor signaling in nonexcitable cells.
  Journal
J Neurobiol 53:524-34 (2002)
DOI:10.1002/neu.10114
Reference
PMID:11923408
  Authors
Araque A, Martin ED, Perea G, Arellano JI, Buno W
  Title
Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices.
  Journal
J Neurosci 22:2443-50 (2002)
DOI:10.1523/JNEUROSCI.22-07-02443.2002
Reference
PMID:12690458
  Authors
Lucas-Meunier E, Fossier P, Baux G, Amar M
  Title
Cholinergic modulation of the cortical neuronal network.
  Journal
Pflugers Arch 446:17-29 (2003)
DOI:10.1007/s00424-002-0999-2
Reference
PMID:20060019
  Authors
Abreu-Villaca Y, Filgueiras CC, Manhaes AC
  Title
Developmental aspects of the cholinergic system.
  Journal
Behav Brain Res 221:367-78 (2011)
DOI:10.1016/j.bbr.2009.12.049
Related
pathway
mcc00564  Glycerophospholipid metabolism
mcc04010  MAPK signaling pathway
mcc04020  Calcium signaling pathway
mcc04721  Synaptic vesicle cycle
mcc04975  Fat digestion and absorption
KO pathway
ko04725   
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