F. Muller et al., PHOSPHORYLATION OF MAMMALIAN OLFACTORY CYCLIC NUCLEOTIDE-GATED CHANNELS INCREASES LIGAND SENSITIVITY, The Journal of neuroscience, 18(1), 1998, pp. 164-173
In vertebrate olfactory sensory neurons, odorant receptors couple the
sensory signal to the synthesis of the second messenger cAMP. Cyclic n
ucleotide-gated (CNG) channels are activated by binding of cAMP and co
nduct a depolarizing receptor current that leads to electrical excitat
ion of the neuron. The sensitivity of olfactory CNG channels for cAMP
can be significantly reduced by binding of calmodulin to a regulatory
domain that resides within the N-terminus of the cr-subunit of the cha
nnel. This regulatory domain also contains a consensus phosphorylation
sequence for protein kinase C (PKC). We have investigated the effect
of channel phosphorylation by PKC and found that phosphorylation incre
ases ligand sensitivity without counteracting modulation of the channe
l by calmodulin. We have identified the amino acid residue that is pho
sphorylated by PKC and have localized three isoforms of PKC in olfacto
ry sensory cilia. The results of this study provide information about
the control of ligand sensitivity in olfactory CNG channels by an intr
insic regulatory domain, representing both a calmodulin-binding site a
nd a substrate for PKC.