Be Fast to Retain Your Identity: The Role of Olfactory Marker Protein in Olfactory Receptor Neurons
Material below summarizes the article The Odorant Receptor-Dependent Role of Olfactory Marker Protein in Olfactory Receptor Neurons, published on March 9, 2016, in JNeurosci and authored by Michele Dibattista and Johannes Reisert.
Animals, in their natural environment, sample their surroundings in search for chemical cues that are crucial for their surviving. Finding food and friends or avoiding foes are only a few of the plethora of behaviors that odorous signals can trigger. These volatile odor cues are detected by olfactory receptor neurons (ORNs) via a signal transduction mechanism that converts chemical information into an electrical signal that is sent to the brain in form of action potentials.
A given ORN expresses only one type of odorant receptor from around a thousand in mice. Odorant receptors (ORs) form the largest family of G protein-coupled receptors in mammal genomes. Activation of an odorant receptor leads, via a G protein, to the activation of adenylyl cyclase and an increase in intracellular cAMP levels. cAMP gates open a cyclic nucleotide-gated channel, which allows Na+ and Ca2+ to enter, with Ca2+ activating an excitatory Ca2+ activated Cl- channel, leading to further depolarization.
Potentially, all these players, from ORs to enzymes and ion channels, can have a basal activity, thus additively contributing transduction activity or “noise” even in the absence of odorants. Surprisingly, in ORNs, all transduction components have little to no basal activity with the exception of the OR, with each OR having its own level of basal activity.
Therefore the chosen OR not only determines which odorants an ORN responds to but also imparts a specific level of basal activity, noise, to the ORN, which manifests itself in different frequencies of action potential firing in the absence of odorant stimulation.
Hence, like other sensory systems ORNs can be intrinsically noisy, in this case depending on the OR expressed. This raises the question what the function and logic of such basal OR-driven activity might be and how noise is minimized throughout olfactory signal transduction components to still allow for appropriate signal detection and the OR to be the dominant source of noise in ORNs?
Our lab focused on olfactory marker protein (OMP), a protein expressed in all mature ORNs, whose function remained mostly elusive although it was discovered 30 years ago.
In our recent paper, we found that knocking out this enigmatic protein abolishes the difference in basal activity in ORNs expressing different ORs and leads to overall elevated levels of cAMP even in the absence of stimulation. cAMP is produced by adenylyl cyclase that can have a high basal activation rate, but OMP ensures that this spontaneous activation rate of adenylyl cyclase is largely suppressed and therefore acts as a “brake” on signal transduction. This allows the OR to remain the main driver and determinant of basal activity.
In this way, the expression of a single OR type with its pivotal role in determining the noise level in an ORN, can play different instructive roles in ORN physiology. For example, the spontaneous firing pattern of an ORN, determined by the expressed OR, may ensure that neurons with similar levels of activity form similar innervation patters in the olfactory bulb (“neurons that that fire together wire together”) to have an instructive role for correct axonal targeting to the olfactory bulb.
OMP achieves the reduction in basal activity by shortening the duration of basal and odorant-evoked activation, as knocking out OMP prolongs ORN responses up to 10-fold. Or in other words, OMP speeds up olfactory signal transduction and therefore the time course of the odorant-induced response. This is an important additional aspect of OMP function as the odor present in the environment changes rapidly in space and time and ORNs should be able to encode for these changes.
Furthermore, mice sample odors by breathing or sniffing up to 10 times per second, imposing a rapid stimulation pattern on ORNs. We found that ORNs can follow rapid stimulation with reasonable fidelity, unless OMP is absent when the response time course is too slow to allow for clear separation between subsequent stimulation and reliable action potential firing in response to each stimulus.
Additionally, OMP also greatly improves the detection of short stimuli, which again is important during short stimulation durations during rapid odorant sampling. This suggests that speeding up of signal transduction by OMP is required for reliable transmission of odor information to the brain.
In conclusion, our paper describes a new key physiological role of OMP in ORNs. The involvement of OMP in cAMP dynamics opens interesting scenarios in cell types other than ORNs since new findings suggest that OMP is also expressed in the bladder, heart, and thyroid.
The Odorant Receptor-Dependent Role of Olfactory Marker Protein in Olfactory Receptor Neurons. Michele Dibattista, Johannes Reisert. The Journal of Neuroscience Mar 2016, 36(10): 2995-3006; DOI: 10.1523/JNEUROSCI.4209-15.2016