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Chapter 52 Molecular Basis of Olfaction and Taste Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 1 FIGURE 52-1: A schematic diagram of the olfactory epithelium. Odorants enter the nasal cavity, diffuse through the nasal mucous and interact with specific receptors on the dendritic cilia of olfactory sensory neurons. The signals initiated by this receptor binding are transduced into electrical signals within the cilia and are transmitted along the sensory neuron axons to the olfactory bulb in the brain. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 2 FIGURE 52-2: Amino acid sequence conservation across mammalian odorant receptors. ORs pass through the plasma membrane (blue box) seven times, with the N-terminus located extracellularly and the C-terminus intracellularly. The degree of conservation of each amino acid in this consensus OR is indicated by a colored ball, with dark blue being most highly conserved and red most highly variable. Source: Modified from Liu et al. (2003) Genomics, 81: 443–456 with permission. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 3 FIGURE 52-3: A model for the transduction of odors in canonical OSNs. The individual steps are detailed in the text. Note that several feedback loops modulate the odor response, including inhibition of the CNG channel by Ca2+ (purple balls) that permeate the channel, and a Ca2+/calmodulin (CaM)-mediated desensitization of the CNG channel that underlies rapid odor adaptation. Several other mechanisms have also been described, including phosphodiesterase-mediated hydrolysis of the second messenger cAMP and phosphorylation of the OR by various kinases. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 4 FIGURE 52-4: A model for chemosensory transduction in vomeronasal sensory neurons. The individual steps are detailed in the text. In contrast to the transduction cascade in OSNs, the mechanism of vomeronasal transduction is less well characterized. Vomeronasal sensory neurons express V1R, V2R or FPR receptors and either Gαi2 or Gαo. The TRPC2 channel subunit is expressed in all VSNs, and may be part of a multimeric channel complex. Ca2+ ions are represented as purple balls; Na+ ions as blue balls. VR, vomeronasal receptor (V1R, V2R or FPR); PIP2, phosphatidylinositol 4,5-bisphosphate; IP 3, inositol 1,4,5-trisphosphate. DAG, diacylglycerol. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 5 FIGURE 52-5: Tongue, taste papillae and taste buds. (A) Surface of the rat tongue showing the location of the taste papillae. (B) Crosssection of the three main types of taste papillae: fungiform, foliate and (circum)vallate. (C) Taste buds contain taste receptor cells (TRCs) and basal cells. Taste receptor proteins present on the microvilli of TRCs respond to tastants in the oral cavity, initiating a transduction cascade that results in the release of neurotransmitter onto afferent cranial nerve fibers, which carry taste information back to the brainstem. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 6 FIGURE 52-6: A model for the major signaling mechanisms for the transduction of sweet, bitter and umami stimuli. The individual steps are detailed in the text. Note that stimuli of each of these taste qualities interact with GPCRs: bitter stimuli with T2Rs, and sweet and umami stimuli with T1Rs. α-Gustducin has been implicated in the transduction of all three types of stimuli, but other α-subunits likely also couple to T1Rs or T2Rs in some TRC populations. PLC-β2 and the Ca2+ -activated TRP channel subunit TRPM5 are essential for normal sweet, bitter and umami taste. The role of IP3 and the IP3R in the stimulus-dependent increase in intracellular Ca2+ as depicted are speculative. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved. 7