PHOSPHORYLATION OF MAMMALIAN OLFACTORY CYCLIC NUCLEOTIDE-GATED CHANNELS INCREASES LIGAND SENSITIVITY

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.