Glatz Molecular Basis of Olfaction

1. Auflage 2015
ISBN: 978-0-12-802913-8
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band Volume 130, 144 Seiten

Reihe: Progress in Molecular Biology and Translational Science

The scope of this volume of Progress in Molecular Biology and Translational Science includes the molecular regulation of olfactory processes in vertebrates and insects including detailed discussion of olfactory proteins, signaling cascades and olfactory receptor modeling. In addition, because insect olfaction is an important and emerging field, it is also discussed in the context of key research questions such as disruption of host-finding by insect disease vectors, elucidation of the diverse range of compounds that are detected by insects, and the detection of pheromones by moths. - Comprehensive coverage of molecular processes in olfaction of vertebrates and insects - Focus on the emerging field of insect olfaction - Contributions by leading research groups in their fields, from a range of countries - Discusses fundamental knowledge and also key applications being addressed by the research

Autoren/Hrsg.

Glatz, Richard

Inhaltsverzeichnis

1;Front Cover;1
2;Molecular Basis of Olfaction;4
3;Copyright;5
4;Contents;6
5;Contributors;8
6;Preface;10
7;Chapter 1: Mammalian Olfactory Receptors: Molecular Mechanisms of Odorant Detection, 3D-Modeling, and Structure-Activity ...;14
7.1;1. Mammalian Olfactory Receptors: From Genes to Proteins;15
7.1.1;1.1. Genes and pseudogenes;15
7.1.2;1.2. OR protein expression;18
7.1.3;1.3. Olfactory signal transduction;20
7.2;2. Olfactory Receptor Activity Regulation: Homodimerization, Binding Cooperativity, and Allostery;22
7.3;3. Olfactory Receptor 3D Modeling and Use for Virtual Screening;25
7.3.1;3.1. Model building;31
7.3.2;3.2. Ligand virtual screening;33
7.3.3;3.3. GPCR inverse agonist, antagonist, and agonist ligands;34
7.4;4. Odorant Ligands Structure-Activity Relationships;36
7.5;References;38
8;Chapter 2: Olfactory Signaling in Insects;50
8.1;1. Introduction;51
8.2;2. Insect Olfactory Receptors;53
8.2.1;2.1. Structure;53
8.2.2;2.2. Function;55
8.2.3;2.3. Regulation;60
8.3;3. Role of Orco;62
8.4;4. Final Remarks;63
8.5;Acknowledgments;63
8.6;References;64
9;Chapter 3: Advances in the Identification and Characterization of Olfactory Receptors in Insects;68
9.1;1. Introduction: The Molecular Bases of Odor Detection in Insects;69
9.2;2. Identification of Complete Insect OR Repertoires Could Only Be Achieved by Genome and Transcriptome Sequencing;71
9.2.1;2.1. Advances in sequencing technologies and bioinformatic tools;72
9.2.2;2.2. Exploitation of insect genomes for OR identification;73
9.2.3;2.3. Developing insect antennal transcriptomes for OR identification;77
9.3;3. Toward the Development of High Throughput Methods for the Functional Characterization of Insect ORs;80
9.3.1;3.1. Description of the different methodologies;80
9.3.1.1;3.1.1. In vitro heterologous expression systems;80
9.3.1.2;3.1.2. In vivo heterologous expression systems;82
9.3.2;3.2. Large OR repertoire deorphanization;83
9.3.3;3.3. Future perspective in the functional characterization of insect ORs;84
9.3.3.1;3.3.1. Automatization for HT screens;85
9.3.3.2;3.3.2. In silico HT screens;85
9.4;4. Conclusion;86
9.5;References;86
10;Chapter 4: Olfactory Disruption: Toward Controlling Important Insect Vectors of Disease;94
10.1;1. Introduction;95
10.2;2. Detection of Olfactory Signals by Insect Vectors;95
10.2.1;2.1. Odorant-binding and chemosensory proteins;97
10.2.2;2.2. Odorant receptors;99
10.2.3;2.3. Gustatory receptors;100
10.2.4;2.4. Ionotropic receptors;100
10.2.5;2.5. Sensory neuron membrane proteins;101
10.2.6;2.6. Activation of olfactory receptor neurons;101
10.2.7;2.7. Processing of olfactory signals in the brain;103
10.2.8;2.8. Volatile sensation in GRNs;106
10.2.9;2.9. Interaction of repellents with olfactory receptors;106
10.3;3. Discovery and Development of New Repellents;109
10.4;4. Conclusion;111
10.5;References;111
11;Chapter 5: Pheromone Reception in Moths: From Molecules to Behaviors;122
11.1;1. Introduction;123
11.2;2. Structure of Antennae;124
11.3;3. Antennal ORNs;124
11.4;4. Molecular Components of Chemical Reception;125
11.5;5. Pheromone Receptors;125
11.6;6. Pheromone-Binding Proteins;128
11.7;7. General Odorant-Binding Proteins;130
11.8;8. Sensory Neuron Membrane Proteins;130
11.9;9. Antennal Lobe;131
11.10;10. Behavior;132
11.11;Acknowledgments;133
11.12;References;133
12;Index;142
13;Color Plate;145

Leseproben

Chapter One Mammalian Olfactory Receptors
Molecular Mechanisms of Odorant Detection, 3D-Modeling, and Structure–Activity Relationships
Marie-Annick Persuy*; Guenhaël Sanz*; Anne Tromelin†; Thierry Thomas-Danguin†; Jean-François Gibrat‡; Edith Pajot-Augy*,1    * INRA UR 1197 NeuroBiologie de l'Olfaction, Domaine de Vilvert, Jouy-en-Josas, France
† INRA UMR 1129 Flaveur, Vision et Comportement du Consommateur, Dijon, France
‡ INRA UR1077 Mathématique Informatique et Génome, Domaine de Vilvert, Jouy-en-Josas, France
1 Corresponding author: email address: [e-mail] Abstract
This chapter describes the main characteristics of olfactory receptor (OR) genes of vertebrates, including generation of this large multigenic family and pseudogenization. OR genes are compared in relation to evolution and among species. OR gene structure and selection of a given gene for expression in an olfactory sensory neuron (OSN) are tackled. The specificities of OR proteins, their expression, and their function are presented. The expression of OR proteins in locations other than the nasal cavity is regulated by different mechanisms, and ORs display various additional functions. A conventional olfactory signal transduction cascade is observed in OSNs, but individual ORs can also mediate different signaling pathways, through the involvement of other molecular partners and depending on the odorant ligand encountered. ORs are engaged in constitutive dimers. Ligand binding induces conformational changes in the ORs that regulate their level of activity depending on odorant dose. When present, odorant binding proteins induce an allosteric modulation of OR activity. Since no 3D structure of an OR has been yet resolved, modeling has to be performed using the closest G-protein-coupled receptor 3D structures available, to facilitate virtual ligand screening using the models. The study of odorant binding modes and affinities may infer best-bet OR ligands, to be subsequently checked experimentally. The relationship between spatial and steric features of odorants and their activity in terms of perceived odor quality are also fields of research that development of computing tools may enhance. Keywords Olfactory receptor proteins Mammals Odorant binding proteins Odorant ligands Dimerization Allosteric modulation 3D-modeling Screening 3D-QSAR modeling 1 Mammalian Olfactory Receptors: From Genes to Proteins
Olfactory receptors are predominantly expressed in the main olfactory epithelium located in the nasal cavity. They are the gateways, located across the plasma membranes of olfactory sensory neurons (OSN) cilia, through which the message conveyed by the odorant molecules in the ambient air transit, before being transduced into an electrical signal. 1.1 Genes and pseudogenes
In mammals, there exist several hundred (up to several thousand) OR genes accounting for 1–3% of estimated mammalian gene repertoire,1,2 and representing the largest gene superfamily. The number of OR genes exceeds 1700 in the rat and is around 860 in humans.3 This abundance is justified by the number of physiological functions in which olfaction is involved (food intake and preferences, search for prey, predator avoidance, social behaviors, mother–young relationships, spatial orientation, stress, etc.), even though this chemical sense was for a while considered to be a minor sense relative to vision. ORs being GPCRs are characterized by seven-transmembrane helices (TMHs), participating in the transmission of the olfactory message carried by the volatile odorant compounds of the environment.4–6 Because ORs are involved in the detection of chemical messages from the environment of animals, their genes have undergone selection pressure, inducing the evolution of the olfactory repertoires of the various species. Some OR genes evolved to nonfunctional pseudogenes7 in varying proportions depending on the species, from ˜ 20% in the mouse and dog8,9 to ˜ 50–60% in primates and humans1,3,10 (for review, see Ref. 11). Indeed, if the number of OR genes differs from species to species (133 ORs in zebrafish to 1300 in pigs,12 2129 in cows, 4200 in African elephants13) the amount of pseudogenes is also variable. Some primates have less than 400 types of functional ORs (humans and chimpanzees, orangutans, and macaques even less14,15) compared to over 1000 for pigs, rodents and dogs,12,16,17 and 1948 in African elephants.13 However, the cognitive power of these species, i.e., the ability to process olfactory data, allows them to integrate information from complex olfactory environments, beyond simply the number of functional ORs that can be activated.18 Mammalian OR genes are organized in a large number of clusters distributed on many chromosomes e.g., 9 chromosomes for mice,19 all chromosomes except 20, and Y for humans.7 Potentially, coding sequences may predominate on some chromosomes (7, 16, and 17 in humans, for instance7). OR pseudogenes are interspersed with full-length OR genes. Closely located OR genes within a cluster tend to be closely related evolutionarily, while duplication of whole OR gene clusters appears to be rare.20 Generation of this large and diverse multigenic family involved in a key biological function may result from successive duplications of large genomic regions during evolution,11,21 followed by an accumulation of mutations. Moreover, evolutionarily distantly related genes may be found in a given OR gene cluster, and OR genes with a close evolutionary relationship may be located at different clusters or chromosomes,20 suggesting additional chromosomal rearrangements within OR gene clusters and shuffling of the genes from different clusters. In different species, a number of OR genes exhibit sequence identities above 90%, for instance in dogs and humans,22 humans and other primates,7,14,23–25 rats and mice.25 Man et al.26 showed that orthologs (coded by genes deriving from the same ancestor by speciation) were more similar than paralogs (coded by genes deriving from the same ancestor gene by duplication) when measuring amino acid similarity, using either the whole coding sequence or the 22 amino acids predicted to be involved in ligand binding. In closely related species, orthologs tend to present similar ligand selectivity but important differences in receptor potency (EC50) to a given ligand. However, while paralogous ORs within the same species respond to a common ligand only 33% of the time, orthologous ORs respond to a common ligand 82% of the time on average (from 93% for human–chimpanzee orthologs to 83% for human–mouse orthologs).25 Moreover, the genetic variation in the coding region of OR genes may contribute to the variation in odor perception among individuals. Mammalian OR genes are divided into two classes. Class I was initially ascribed to fish OR genes for which OR proteins mostly bind hydrophilic odorants (amino acids), while Class II was related to mammalian OR genes with OR proteins binding hydrophobic odorants. In fact, recent studies show that Class I ORs can be subdivided into several groups, among which the a group is proposed to encode ORs specific to airborne odorants, while the d, ?, ?, and ? group genes appear to primarily detect water-soluble odorants. Only the a group of Class I is present in mammals, together with the Class II genes (which consists only of ? group genes).27 Fishes encode only Class I genes, of groups d, ?, ?, and ?, and in amphibians OR genes are found from both Classes (Fig. 1). Interestingly, both in the human and mouse genomes, all Class I OR genes (thus of the a group) are encoded in a single genomic cluster, contrary to Class II genes.11,28 Pseudogenes are present in a lower proportion among human Class I ORs (52%) than Class II ORs (77%),1 suggesting that “fish” OR genes still have a functional significance. Figure 1 Evolutionary dynamics of OR genes: a phylogenetic tree of OR genes from five vertebrate species. The genes that belong to different groups are represented by different colored triangles. The size of each triangle is approximately proportional to the number of OR genes from each species. The a and ? group genes are proposed to primarily detect airborne odorants because they exist in tetrapods, whereas the d, , ?, and ? group genes that exist in fishes and Xenopus appear to primarily detect water-soluble odorants. The functions of the group ß, ?, and ? genes are unclear. Adapted by permission from Macmillan Publishers Ltd. Nature Reviews Genetics, Ref. 29 copyright 2008. OR genes exhibit a relatively well-conserved structure including one or several small untranslated exons at their 5' termini, followed by a large 3–10 kb intron preceding a single coding exon of...