Olfactory transduction - Pan troglodytes (chimpanzee)

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.Longer exposure to odorants can stimulate particulate guanylyl cyclase in cilia to produce cGMP and activate PKG, leading to a further increase in amount and duration of intracellular cAMP levels, which may serve to convert inactive forms of protein kinase A (PKA2) to active forms (PKA*). As part of a feedback loop, PKA can inhibit the activation of particulate guanylyl cyclase.

Organismal Systems; Sensory system

Pan troglodytes (chimpanzee) [GN:ptr]

PMID:11557990

Firestein S.

How the olfactory system makes sense of scents.

Nature 413:211-8 (2001)

PMID:16269360

Ache BW, Young JM.

Olfaction: diverse species, conserved principles.

Neuron 48:417-30 (2005)

PMID:10908849

Nakamura T.

Cellular and molecular constituents of olfactory sensation in vertebrates.

Comp Biochem Physiol A Mol Integr Physiol 126:17-32 (2000)

PMID:10944513

Zufall F, Leinders-Zufall T.

The cellular and molecular basis of odor adaptation.

Chem Senses 25:473-81 (2000)

PMID:9547228

Moon C, Jaberi P, Otto-Bruc A, Baehr W, Palczewski K, Ronnett GV.

Calcium-sensitive particulate guanylyl cyclase as a modulator of cAMP in olfactory receptor neurons.

J Neurosci 18:3195-205 (1998)

PMID:11826268

Ronnett GV, Moon C.

G proteins and olfactory signal transduction.

Annu Rev Physiol 64:189-222 (2002)

PMID:12939389

Barry PH.

The relative contributions of cAMP and InsP3 pathways to olfactory responses in vertebrate olfactory receptor neurons and the specificity of odorants for both pathways.

J Gen Physiol 122:247-50 (2003)

PMID:12488531

Kohout TA, Lefkowitz RJ.

Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization.

Mol Pharmacol 63:9-18 (2003)

PMID:9020189

Boekhoff I, Touhara K, Danner S, Inglese J, Lohse MJ, Breer H, Lefkowitz RJ.

Phosducin, potential role in modulation of olfactory signaling.

J Biol Chem 272:4606-12 (1997)