scholarly journals Odorant and Taste Receptors in Sperm Chemotaxis and Cryopreservation: Roles and Implications in Sperm Capacitation, Motility and Fertility

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 488
Author(s):  
Malik Ahsan Ali ◽  
Yihan Wang ◽  
Ziyue Qin ◽  
Xiang Yuan ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Sperm Quality ◽  
Freeze Tolerance ◽  
G Protein Coupled Receptors ◽  
Odorant Receptors ◽  
Taste Receptors ◽  
Sperm Capacitation ◽  
Sperm Chemotaxis ◽  
Acrosomal Reaction ◽  
Cl Channels ◽  
G Protein Coupled

Sperm chemotaxis, which guide sperm toward oocyte, is tightly associated with sperm capacitation, motility, and fertility. However, the molecular mechanism of sperm chemotaxis is not known. Reproductive odorant and taste receptors, belong to G-protein-coupled receptors (GPCR) super-family, cause an increase in intracellular Ca2+ concentration which is pre-requisite for sperm capacitation and acrosomal reaction, and result in sperm hyperpolarization and increase motility through activation of Ca2+-dependent Cl¯ channels. Recently, odorant receptors (ORs) in olfactory transduction pathway were thought to be associated with post-thaw sperm motility, freeze tolerance or freezability and cryo-capacitation-like change during cryopreservation. Investigation of the roles of odorant and taste receptors (TRs) is important for our understanding of the freeze tolerance or freezability mechanism and improve the motility and fertility of post-thaw sperm. Here, we reviewed the roles, mode of action, impact of odorant and taste receptors on sperm chemotaxis and post-thaw sperm quality.

scholarly journals Beyond the Flavour: The Potential Druggability of Chemosensory G Protein-Coupled Receptors

2019 ◽  
Vol 20 (6) ◽  
pp. 1402 ◽  
Author(s):  
Antonella Di Pizio ◽  
Maik Behrens ◽  
Dietmar Krautwurst
Keyword(s):  
G Protein ◽  
Drug Targets ◽  
Current Knowledge ◽  
Chemical Space ◽  
G Protein Coupled Receptors ◽  
The Body ◽  
Odorant Receptors ◽  
Taste Receptors ◽  
Umami Taste ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) belong to the largest class of drug targets. Approximately half of the members of the human GPCR superfamily are chemosensory receptors, including odorant receptors (ORs), trace amine-associated receptors (TAARs), bitter taste receptors (TAS2Rs), sweet and umami taste receptors (TAS1Rs). Interestingly, these chemosensory GPCRs (csGPCRs) are expressed in several tissues of the body where they are supposed to play a role in biological functions other than chemosensation. Despite their abundance and physiological/pathological relevance, the druggability of csGPCRs has been suggested but not fully characterized. Here, we aim to explore the potential of targeting csGPCRs to treat diseases by reviewing the current knowledge of csGPCRs expressed throughout the body and by analysing the chemical space and the drug-likeness of flavour molecules.

scholarly journals Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Neil N. Patel ◽  
Alan D. Workman ◽  
Noam A. Cohen
Keyword(s):  
Airway Epithelium ◽  
Taste Receptor ◽  
Upper Airway ◽  
Airway Disease ◽  
G Protein Coupled Receptors ◽  
Innate Immune ◽  
Taste Receptors ◽  
Taste Sensation ◽  
G Protein Coupled

Evidence is emerging that shows taste receptors serve functions outside of taste sensation of the tongue. Taste receptors have been found in tissue across the human body, including the gastrointestinal tract, bladder, brain, and airway. These extraoral taste receptors appear to be important in modulating the innate immune response through detection of pathogens. This review discusses taste receptor signaling, focusing on the G-protein–coupled receptors that detect bitter and sweet compounds in the upper airway epithelium. Emphasis is given to recent studies which link the physiology of sinonasal taste receptors to clinical manifestation of upper airway disease.

scholarly journals The cell biology of smell

2010 ◽  
Vol 191 (3) ◽  
pp. 443-452 ◽  
Author(s):  
Shannon DeMaria ◽  
John Ngai
Keyword(s):  
Olfactory System ◽  
Cell Biology ◽  
Odorant Receptor ◽  
Large Family ◽  
G Protein Coupled Receptors ◽  
Odorant Receptors ◽  
Chemical Structures ◽  
Wide Range ◽  
G Protein Coupled ◽  
The Brain

The olfactory system detects and discriminates myriad chemical structures across a wide range of concentrations. To meet this task, the system utilizes a large family of G protein–coupled receptors—the odorant receptors—which are the chemical sensors underlying the perception of smell. Interestingly, the odorant receptors are also involved in a number of developmental decisions, including the regulation of their own expression and the patterning of the olfactory sensory neurons' synaptic connections in the brain. This review will focus on the diverse roles of the odorant receptor in the function and development of the olfactory system.

scholarly journals G Protein-Coupled Receptors in Taste Physiology and Pharmacology

2020 ◽  
Vol 11 ◽  
Author(s):  
Raise Ahmad ◽  
Julie E. Dalziel
Keyword(s):  
Binding Site ◽  
G Protein ◽  
Molecular Mechanisms ◽  
Taste Receptor ◽  
Receptor Activation ◽  
G Protein Coupled Receptors ◽  
Type I ◽  
Taste Receptors ◽  
Agonist Binding ◽  
G Protein Coupled

Heterotrimeric G protein-coupled receptors (GPCRs) comprise the largest receptor family in mammals and are responsible for the regulation of most physiological functions. Besides mediating the sensory modalities of olfaction and vision, GPCRs also transduce signals for three basic taste qualities of sweet, umami (savory taste), and bitter, as well as the flavor sensation kokumi. Taste GPCRs reside in specialised taste receptor cells (TRCs) within taste buds. Type I taste GPCRs (TAS1R) form heterodimeric complexes that function as sweet (TAS1R2/TAS1R3) or umami (TAS1R1/TAS1R3) taste receptors, whereas Type II are monomeric bitter taste receptors or kokumi/calcium-sensing receptors. Sweet, umami and kokumi receptors share structural similarities in containing multiple agonist binding sites with pronounced selectivity while most bitter receptors contain a single binding site that is broadly tuned to a diverse array of bitter ligands in a non-selective manner. Tastant binding to the receptor activates downstream secondary messenger pathways leading to depolarization and increased intracellular calcium in TRCs, that in turn innervate the gustatory cortex in the brain. Despite recent advances in our understanding of the relationship between agonist binding and the conformational changes required for receptor activation, several major challenges and questions remain in taste GPCR biology that are discussed in the present review. In recent years, intensive integrative approaches combining heterologous expression, mutagenesis and homology modeling have together provided insight regarding agonist binding site locations and molecular mechanisms of orthosteric and allosteric modulation. In addition, studies based on transgenic mice, utilizing either global or conditional knock out strategies have provided insights to taste receptor signal transduction mechanisms and their roles in physiology. However, the need for more functional studies in a physiological context is apparent and would be enhanced by a crystallized structure of taste receptors for a more complete picture of their pharmacological mechanisms.

scholarly journals Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors

2020 ◽  
Vol 117 (6) ◽  
pp. 2957-2967
Author(s):  
Kentaro Ikegami ◽  
Claire A. de March ◽  
Maira H. Nagai ◽  
Soumadwip Ghosh ◽  
Matthew Do ◽  
...  
Keyword(s):  
Cell Surface ◽  
G Protein ◽  
Surface Expression ◽  
Structural Instability ◽  
G Protein Coupled Receptors ◽  
Machine Learning Techniques ◽  
Odorant Receptors ◽  
Cell Surface Expression ◽  
Conserved Residues ◽  
G Protein Coupled

Mammalian odorant receptors are a diverse and rapidly evolving set of G protein-coupled receptors expressed in olfactory cilia membranes. Most odorant receptors show little to no cell surface expression in nonolfactory cells due to endoplasmic reticulum retention, which has slowed down biochemical studies. Here we provide evidence that structural instability and divergence from conserved residues of individual odorant receptors underlie intracellular retention using a combination of large-scale screening of odorant receptors cell surface expression in heterologous cells, point mutations, structural modeling, and machine learning techniques. We demonstrate the importance of conserved residues by synthesizing consensus odorant receptors that show high levels of cell surface expression similar to conventional G protein-coupled receptors. Furthermore, we associate in silico structural instability with poor cell surface expression using molecular dynamics simulations. We propose an enhanced evolutionary capacitance of olfactory sensory neurons that enable the functional expression of odorant receptors with cryptic mutations.

scholarly journals Solitary chemosensory cells in the respiratory and vomeronasal epithelium of the human nose: a pilot study

2011 ◽  
Vol 49 (5) ◽  
pp. 507-512
Author(s):  
Thomas Braun ◽  
Brigitte Mack ◽  
Matthias F. Kramer
Keyword(s):  
G Protein ◽  
Bitter Taste ◽  
Vomeronasal Organ ◽  
G Protein Coupled Receptors ◽  
Taste Receptors ◽  
Tissue Samples ◽  
Taste Transduction ◽  
Solitary Chemosensory Cells ◽  
G Protein Coupled ◽  
Human Nose

Background: Recently, solitary chemosensory cells have been described in the respiratory and vomeronasal epithelium of the rodent nose. Expressing G-protein coupled receptors for sweet, umami and bitter taste transduction, these cells are thought to mediate trigeminal reflexes upon stimulation with chemical irritants. The present study analyzes human nasal mucosa for the presence of solitary chemosensory cells. Methodology: In human tissue samples from respiratory mucosa and the vomeronasal organ, gene expression of taste receptors families was studied in five patients using the Affymetrix Human Gene 1.0 ST Array and immunohistochemistry with specific antibodies. Results: Immunohistochemistry revealed that solitary chemosensory cells expressing G-protein coupled receptors for sweet, umami and bitter taste transduction are present in the human nose. cDNA microarray analysis congruently showed that cells expressing bitter taste receptors accumulate in the vomeronasal organ compared to the respiratory epithelium. Conclusions: Solitary chemosensory cells expressing taste receptors are also present in the human nose. Since they are thought to mediate trigeminal reflexes, their role in the pathogenesis of nasal hyperreagibility should be elucidated in further studies.

scholarly journals Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors

2019 ◽  
Author(s):  
Kentaro Ikegami ◽  
Claire A. de March ◽  
Maira H. Nagai ◽  
Soumadwip Ghosh ◽  
Matthew Do ◽  
...  
Keyword(s):  
Cell Surface ◽  
G Protein ◽  
Surface Expression ◽  
Structural Instability ◽  
G Protein Coupled Receptors ◽  
Odorant Receptors ◽  
Cell Surface Expression ◽  
Conserved Residues ◽  
Olfactory Cells ◽  
G Protein Coupled

AbstractMammalian odorant receptors are a diverse and rapidly evolving set of G protein-coupled receptors expressed in olfactory cilia membranes. Most odorant receptors show little to no cell surface expression in non-olfactory cells due to endoplasmic reticulum retention, which has slowed down biochemical studies. Here, we provide evidence that structural instability and divergence from conserved residues of individual odorant receptors underlie intracellular retention using a combination of large-scale screening of odorant receptors cell surface expression in heterologous cells, point mutations, structural modeling, and machine learning techniques. We demonstrate the importance of conserved residues by synthesizing “consensus” odorant receptors that show high levels of cell surface expression similar to conventional G protein-coupled receptors. Furthermore, we associate in silico structural instability with poor cell surface expression using molecular dynamics simulations. We propose an enhanced evolutionary capacitance of olfactory sensory neurons that enable the functional expression of odorant receptors with cryptic mutations.Significance StatementOdor detection in mammals depends on the largest family of G protein-coupled receptors, the odorant receptors, which represent ∼2% of our protein-coding genes. The vast majority of odorant receptors are trapped within the cell when expressed in non-olfactory cells. The underlying causes of why odorant receptors cannot be functionally expressed in non-olfactory cells have remained enigmatic for over 20 years. Our study points to divergence from a consensus sequence as a key factor in a receptor’s inability to function in non-olfactory cells, which in turn, helps explain odorant receptors’ exceptional functional diversity and rapid evolution. We also show the success of protein engineering strategies for promoting odorant receptor cell surface expression.

scholarly journals Natural Compounds as Guides for the Discovery of Drugs Targeting G-Protein-Coupled Receptors

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5060
Author(s):  
Joan Serrano-Marín ◽  
Irene Reyes-Resina ◽  
Eva Martínez-Pinilla ◽  
Gemma Navarro ◽  
Rafael Franco
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
G Protein ◽  
Natural Compounds ◽  
G Protein Coupled Receptors ◽  
Taste Receptors ◽  
Allosteric Modulators ◽  
Chemical Structures ◽  
Therapeutic Drugs ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs), which constitute the most populous family of the human proteome, are the target of 35–45% of approved therapeutic drugs. This review focuses on natural products (excluding peptides) that target GPCRs. Natural compounds identified so far as agonists, antagonists or allosteric modulators of GPCRs have been found in all groups of existing living beings according to Whittaker’s Five Kingdom Classification, i.e., bacteria (monera), fungi, protoctists, plants and animals. Terpenoids, alkaloids and flavonoids are the most common chemical structures that target GPCRs whose endogenous ligands range from lipids to epinephrine, from molecules that activate taste receptors to molecules that activate smell receptors. Virtually all of the compounds whose formula is displayed in this review are pharmacophores with potential for drug discovery; furthermore, they are expected to help expand the number of GPCRs that can be considered as therapeutic targets.

scholarly journals BitterMatch: Recommendation systems for matching molecules with bitter taste receptors

2022 ◽  
Author(s):  
Eitan Margulis ◽  
Yuli Slavutsky ◽  
Tatjana Lang ◽  
Mike Behrens ◽  
Yuval Benjamini ◽  
...  
Keyword(s):  
Experimental Data ◽  
Bitter Taste ◽  
Recommendation Systems ◽  
G Protein Coupled Receptors ◽  
Taste Receptors ◽  
Drug Compliance ◽  
G Protein Coupled ◽  
Hybrid Recommendation

Bitterness is an aversive cue elicited by thousands of chemically diverse compounds. Bitter taste may prevent consumption of foods and jeopardize drug compliance. The G protein-coupled receptors for bitter taste, TAS2Rs, have species-dependent number of subtypes and varying expression levels in extraoral tissues. Molecular recognition by TAS2R subtypes is physiologically important, and presents a challenging case study for ligand-receptor matchmaking. Inspired by hybrid recommendation systems, we developed a new set of similarity features, and created the BitterMatch algorithm that predicts associations of ligands to receptors with ~80% precision at ~50% recall. Associations for several compounds were tested in-vitro, resulting in 80% precision and 42% recall. The encouraging performance was achieved by including receptor properties and integrating experimentally determined ligand-receptor associations with chemical ligand-to-ligand similarities. BitterMatch can predict off-targets for bitter drugs, identify novel ligands and guide flavor design. Inclusion of neighbor-informed similarities improves as experimental data mounts, and provides a generalizable framework for molecule-biotarget matching.

Sign in / Sign up

Export Citation Format

Share Document