KEGG   PATHWAY: ko04740
Entry
ko04740                     Pathway                                
Name
Olfactory transduction
Description
Within the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be transmitted to the brain. Odorant molecules bind to a receptor protein (R) coupled to an olfactory specific Gs-protein (G) and activate a type III adenylyl cyclase (AC), increasing intracellular cAMP levels. cAMP targets an olfactory-specific cyclic-nucleotide gated ion channel (CNG), allowing cations, particularly Na and Ca, to flow down their electrochemical gradients into the cell, depolarizing the ORN. Furthermore, the Ca entering the cell is able to activate a Ca-activated Cl channel, which would allow Cl to flow out of the cell, thus further increasing the depolarization. Elevated intracellular Ca causes adaptation by at least two different molecular steps: inhibition of the activity of adenylyl cyclase via CAMKII-dependent phosphorylation and down-regulation of the affinity of the CNG channel to cAMP.
Class
Organismal Systems; Sensory system
Pathway map
ko04740  Olfactory transduction
ko04740

Other DBs
GO: 0007608
Orthology
K00910  ADRBK, GRK; beta-adrenergic-receptor kinase [EC:2.7.11.15]
K02183  CALM; calmodulin
K04257  OLFR; olfactory receptor
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04439  ARRB; beta-arrestin
K04515  CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K04536  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04543  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04547  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04633  GNAL; guanine nucleotide-binding protein G(olf) subunit alpha
K04949  CNGA2; cyclic nucleotide gated channel alpha 2
K04950  CNGA3; cyclic nucleotide gated channel alpha 3
K04951  CNGA4; cyclic nucleotide gated channel alpha 4
K04952  CNGB1; cyclic nucleotide gated channel beta 1
K05849  SLC8A, NCX; solute carrier family 8 (sodium/calcium exchanger)
K07376  PRKG1; cGMP-dependent protein kinase 1 [EC:2.7.11.12]
K08043  ADCY3; adenylate cyclase 3 [EC:4.6.1.1]
K12321  GUCY2D_E; guanylate cyclase 2D/E [EC:4.6.1.2]
K13752  SLC24A4, NCKX4; solute carrier family 24 (sodium/potassium/calcium exchanger), member 4
K13755  PDE1; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase [EC:3.1.4.17]
K18154  RGS2; regulator of G-protein signaling 2
K18283  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase [EC:3.1.4.17]
K19477  PRKG2; cGMP-dependent protein kinase 2 [EC:2.7.11.12]
K19497  ANO2, TMEM16B; anoctamin-2
K19695  NCALD; neurocalcin delta
Compound
C00020  AMP
C00076  Calcium cation
C00144  GMP
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C00698  Cl-
C00942  3',5'-Cyclic GMP
C01330  Sodium cation
Reference
  Authors
Kaupp UB
  Title
Olfactory signalling in vertebrates and insects: differences and commonalities.
  Journal
Nat Rev Neurosci 11:188-200 (2010)
DOI:10.1038/nrn2789
Reference
  Authors
Peterlin Z, Firestein S, Rogers ME
  Title
The state of the art of odorant receptor deorphanization: a report from the orphanage.
  Journal
J Gen Physiol 143:527-42 (2014)
DOI:10.1085/jgp.201311151
Reference
  Authors
Kato A, Touhara K
  Title
Mammalian olfactory receptors: pharmacology, G protein coupling and desensitization.
  Journal
Cell Mol Life Sci 66:3743-53 (2009)
DOI:10.1007/s00018-009-0111-6
Reference
  Authors
Firestein S.
  Title
How the olfactory system makes sense of scents.
  Journal
Nature 413:211-8 (2001)
DOI:10.1038/35093026
Reference
  Authors
Ache BW, Young JM.
  Title
Olfaction: diverse species, conserved principles.
  Journal
Neuron 48:417-30 (2005)
DOI:10.1016/j.neuron.2005.10.022
Reference
  Authors
Zufall F, Leinders-Zufall T.
  Title
The cellular and molecular basis of odor adaptation.
  Journal
Chem Senses 25:473-81 (2000)
DOI:10.1093/chemse/25.4.473
Reference
  Authors
Lodovichi C, Belluscio L
  Title
Odorant receptors in the formation of the olfactory bulb circuitry.
  Journal
Physiology (Bethesda) 27:200-12 (2012)
DOI:10.1152/physiol.00015.2012
Reference
  Authors
Kohout TA, Lefkowitz RJ.
  Title
Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization.
  Journal
Mol Pharmacol 63:9-18 (2003)
DOI:10.1124/mol.63.1.9
Reference
  Authors
De Palo G, Boccaccio A, Miri A, Menini A, Altafini C
  Title
A dynamical feedback model for adaptation in the olfactory transduction pathway.
  Journal
Biophys J 102:2677-86 (2012)
DOI:10.1016/j.bpj.2012.04.040
Reference
  Authors
Zufall F, Munger SD
  Title
Receptor guanylyl cyclases in mammalian olfactory function.
  Journal
Mol Cell Biochem 334:191-7 (2010)
DOI:10.1007/s11010-009-0325-9
Reference
  Authors
Duda T, Sharma RK
  Title
Ca2+-modulated ONE-GC odorant signal transduction.
  Journal
FEBS Lett 583:1327-30 (2009)
DOI:10.1016/j.febslet.2009.03.036
Related
pathway
ko00230  Purine metabolism
ko04024  cAMP signaling pathway

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