Olfactory receptor neurons signal transduction

Fadool, D. A. and Ache, B. W., Plasma membrane inositol 1,4,5-trisphosphate-activated channels mediate signal transduction in lobster olfactory receptor neurons, Neuron, 9, 907, 1992. 

As is the case for all sensory pathways, the capacity to perceive and respond to olfactory cues (odorants) is the combined result of events that take place in both peripheral and central processing centers. These steps, which will be discussed in detail below, begin with the molecular transduction of chemical signals in the form of odorants into electrical activity by olfactory receptor neurons (ORNs) in the periphery whose axonal projections form characteristic synaptic connections with elements of the central nervous system (CNS). Within the CNS, complex patterns of olfactory signals are integrated and otherwise processed to afford recognition and ultimately, the behavioral responses to the insect s chemical environment. Within the context of pheromone recognition these responses would likely be centered on various elements of the insect s reproductive cycle. 

What happens at the instant when an odor-active molecule comes in touch with our nasal cavity 205 The first interaction of odorant molecules takes place in the olfactory receptor neurons, which are embedded in the pseudostratified columnar epithelium (or simply, olfactory epithelium), which is located in the posterior nasal cavity in the case of mammals. Olfactory sensory neurons express receptor proteins on the surface membrane of the cilia, which gain access to the extracellular region covered with mucus. The airborne odorants are dissolved into the mucus, bind with the receptors, and then the receptor protein triggers a signal transduction cascade. This results in the opening of the cation channel that would depolarize the sensory neuron and eventually elicit a train of action potentials in the axon. The olfactory axon leads to the olfactory bulb through basal lamina and lamina propria. 

Michel WC (1999) Cyclic nucleotide-gated channel activation is not required for activity-dependent labeling of zebrafish olfactory receptor neurons by amino adds. Biol Signals Recept 8 338-347 Michel WC, Derbidge DS (1997) Evidence of distinct amino acid and bile salt receptors in the olfactory system of the zebrafish, Danio rerio. Brain Res 764 179-187 Michel WC, Sanderson MJ, Olson JK, Lipschitz DL (2003) Evidence of a novel transduction pathway mediating detection of polyamines by the zebrafish olfactory system. J Exp Biiol 206 1697-1706... 

Breer H., Sense of smell Signal recognition and transduction in olfactory receptor neurons, in Handbook of Biosensors and Electronic Noses Medicine, Food and Environment, ed. E. Kress-Rogers (Boca Raton, EL CRC Press, 1997, 521-532). 

Mammalian pheromones released into their environment can readily reach their target tissue, either the main olfactory epithelium (MOE) or the VNO. Both target tissues are lined with an olfactory neuroepithelium that contains membrane-bound receptor proteins, which comprise the largest known family of G-protein-coupled [262] receptors in mammals. The number of mammalian olfactory receptors [263-265] found has been astonishing, but not unreasonable. The MOE and VNO have some common features, but also significant difierences in neuron types, primary structures of receptor proteins and signal transduction [266]. 

Insect perception of volatile semiochemicals is mediated through olfactory sensilla, located mainly on the antennae. These sensilla have a porous cuticular surface through which semiochemicals can pass and make contact with the sensillum lymph. Semiochemicals are usually hydrophobic, organic chemicals. For land-living insects, these molecules must be transferred across the aqueous lymph to membrane-bound G-protein-coupled receptors (GPCRs) on the olfactory neurones, from which signal transduction occurs.Transfer across the sensillum lymph is an evolutionary adaptation to terrestrial habitation and is mediated by odorant-binding proteins (OBPs). These are small (14-20 kDa), acidic. 

Figure 2 Depiction of some components of the vertebrate olfactory epithelium in the nose. Odorants, e.g., carvone, deposit themselves in the mucous layer and interact with molecular receptors in the membrane of cilia of the olfactory receptor cells. Subsequent to intracellular signal transduction events, action potentials are sent via the olfactory axons to the olfactory bulbs in the brain. Supporting cells provide physical and physiological support for the olfactory neurons. Undifferentiated basal (stem) cells are the source of new supporting and olfactory receptor cells.

Some olfactory neurons may use a second transduction mechanism. They have receptors coupled through G proteins to PLC rather than to adenylyl cyclase. Signal reception in these cells triggers production of IP3 (Fig. 12-19), which opens IP3-gated Ca2+ channels in the ciliary membrane. Influx of Ca2+ then depolarizes the ciliary membrane and generates a receptor potential or regulates Ca2+-dependent enzymes in the olfactory pathway. 

Ache and coworkers demonstrated that both cyclic nucleotides and inositol phosphates mediate the transduction of environmental chemical signals by the olfactory neurons of P. argus.62 65 Both biochemical and molecular biological techniques have shown that the receptor cells contain various G-protein subunits that would be necessary for signal detection by G-protein-associated chemoreceptors.48 49 66-69 In combination with electrophysiological studies,... 

Very recent efforts to further evaluate the functional implications of phosphoinositol signaling in vertebrate chemosensory transduction have led to the discovery that not only the phosphoinositol breakdown pathway catalyzed by phospholipase C, but also membrane phosphoinositols themselves involving phosphoinositide-3-kinase may play a functional role in the transduction process. It was found that 3-phosphoinositides signaling in concert with the canonical phosphoinositide turnover pathway modulate the cyclic nucleotide signaling cascade downstream of the receptor. The data suggest that 3-phosphoinositide, the primary product of PI3K activity, attenuates the cyclic nucleotide-dependent excitation of olfactory neurons (Spehr et al., 2002). 

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