G-protein coupled receptors Mc4r and Drd1a can serve as surrogate odorant receptors in mouse olfactory sensory neurons. 2018

Markella Katidou, and Xavier Grosmaitre, and Jiangwei Lin, and Peter Mombaerts
Max Planck Research Unit for Neurogenetics, Frankfurt, Germany.

In the mouse, most mature olfactory sensory neurons (OSNs) express one allele of one gene from the repertoire of ~1100 odorant receptor (OR) genes, which encode G-protein coupled receptors (GPCRs). Axons of OSNs that express a given OR coalesce into homogeneous glomeruli, which reside at conserved positions in the olfactory bulb. ORs are intimately involved in ensuring the expression of one OR per OSN and the coalescence of OSN axons into glomeruli. But the mechanisms whereby ORs accomplish these diverse functions remain poorly understood. An experimental approach that has been informative is to substitute an OR genetically with another GPCR that is normally not expressed in OSNs, in order to determine in which aspects this GPCR can serve as surrogate OR in mouse OSNs. Thus far only the β2-adrenergic receptor (β2AR, Ardb2) has been shown to be able to serve as surrogate OR in OSNs; the β2AR could substitute for the M71 OR in all aspects examined. Can other non-olfactory GPCRs function equally well as surrogate ORs in OSNs? Here, we have generated and characterized two novel gene-targeted mouse strains in which the mouse melanocortin 4 receptor (Mc4r) or the mouse dopamine receptor D1 (Drd1a) is coexpressed with tauGFP in OSNs that express the OR locus M71. These alleles and strains are abbreviated as Mc4r → M71-GFP and Drd1a → M71-GFP. We detected strong Mc4r or Drd1a immunoreactivity in axons and dendritic knobs and cilia of OSNs that express Mc4r or Drd1a from the M71 locus. These OSNs responded physiologically to cognate agonists for Mc4r (Ro27-3225) or Drd1a (SKF81297), and not to the M71 ligand acetophenone. Axons of OSNs expressing Mc4r → M71-GFP coalesced into glomeruli. Axons of OSNs expressing Drd1a → M71-GFP converged onto restricted areas of the olfactory bulb but did not coalesce into glomeruli. Thus, OR functions in OSNs can be substituted by Mc4r or Drd1a, but not as well as by β2AR. We attribute the weak performance of Drd1a as surrogate OR to poor OSN maturation.

UI MeSH Term Description Entries
D008164 Luminescent Proteins Proteins which are involved in the phenomenon of light emission in living systems. Included are the "enzymatic" and "non-enzymatic" types of system with or without the presence of oxygen or co-factors. Bioluminescent Protein,Bioluminescent Proteins,Luminescent Protein,Photoprotein,Photoproteins,Protein, Bioluminescent,Protein, Luminescent,Proteins, Bioluminescent,Proteins, Luminescent
D009830 Olfactory Bulb Ovoid body resting on the CRIBRIFORM PLATE of the ethmoid bone where the OLFACTORY NERVE terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose DENDRITES the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the VOMERONASAL ORGAN via the vomeronasal nerve, is also included here. Accessory Olfactory Bulb,Olfactory Tract,Bulbus Olfactorius,Lateral Olfactory Tract,Main Olfactory Bulb,Olfactory Glomerulus,Accessory Olfactory Bulbs,Bulb, Accessory Olfactory,Bulb, Main Olfactory,Bulb, Olfactory,Bulbs, Accessory Olfactory,Bulbs, Main Olfactory,Bulbs, Olfactory,Glomerulus, Olfactory,Lateral Olfactory Tracts,Main Olfactory Bulbs,Olfactorius, Bulbus,Olfactory Bulb, Accessory,Olfactory Bulb, Main,Olfactory Bulbs,Olfactory Bulbs, Accessory,Olfactory Bulbs, Main,Olfactory Tract, Lateral,Olfactory Tracts,Olfactory Tracts, Lateral,Tract, Lateral Olfactory,Tract, Olfactory,Tracts, Lateral Olfactory,Tracts, Olfactory
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001369 Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Axon
D017447 Receptors, Dopamine D1 A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES. Dopamine D1 Receptors,Dopamine-D1 Receptor,D1 Receptors, Dopamine,Dopamine D1 Receptor,Receptor, Dopamine-D1
D044105 Receptor, Melanocortin, Type 4 A melanocortin receptor subtype found primarily in BRAIN. It shows specificity for ALPHA-MSH; BETA-MSH and ADRENOCORTICOTROPIC HORMONE. Melanocortin Receptor 4,MC4 Receptor,Melanocortin 4 Receptor,Melanocortin-4 Receptor,Receptor, Melanocortin-4,Receptor 4, Melanocortin,Receptor, MC4,Receptor, Melanocortin 4
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018034 Olfactory Receptor Neurons Neurons in the OLFACTORY EPITHELIUM with proteins (RECEPTORS, ODORANT) that bind, and thus detect, odorants. These neurons send their DENDRITES to the surface of the epithelium with the odorant receptors residing in the apical non-motile cilia. Their unmyelinated AXONS synapse in the OLFACTORY BULB of the BRAIN. Neurons, Olfactory Receptor,Olfactory Receptor Cells,Olfactory Receptor Neuron,Olfactory Sensory Cells,Olfactory Sensory Cilia,Olfactory Sensory Neurons,Cell, Olfactory Receptor,Cell, Olfactory Sensory,Cells, Olfactory Receptor,Cells, Olfactory Sensory,Cilia, Olfactory Sensory,Cilias, Olfactory Sensory,Neuron, Olfactory Receptor,Neuron, Olfactory Sensory,Neurons, Olfactory Sensory,Olfactory Receptor Cell,Olfactory Sensory Cell,Olfactory Sensory Cilias,Olfactory Sensory Neuron,Receptor Cell, Olfactory,Receptor Cells, Olfactory,Receptor Neuron, Olfactory,Receptor Neurons, Olfactory,Sensory Cell, Olfactory,Sensory Cells, Olfactory,Sensory Cilia, Olfactory,Sensory Cilias, Olfactory,Sensory Neuron, Olfactory,Sensory Neurons, Olfactory
D018035 Receptors, Odorant Proteins, usually projecting from the cilia of olfactory receptor neurons, that specifically bind odorant molecules and trigger responses in the neurons. The large number of different odorant receptors appears to arise from several gene families or subfamilies rather than from DNA rearrangement. Odorant Receptors,Olfactory Receptor Proteins,Odor Receptor Protein,Odorant Receptor,Olfactory Receptor,Olfactory Receptor Protein,Olfactory Receptors,Receptor Proteins, Odorant,Receptor Proteins, Olfactory,Odorant Receptor Proteins,Protein, Odor Receptor,Protein, Olfactory Receptor,Proteins, Odorant Receptor,Proteins, Olfactory Receptor,Receptor Protein, Odor,Receptor Protein, Olfactory,Receptor, Odorant,Receptor, Olfactory,Receptors, Olfactory
D018343 Receptors, Adrenergic, beta-2 A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-2 receptors are more sensitive to EPINEPHRINE than to NOREPINEPHRINE and have a high affinity for the agonist TERBUTALINE. They are widespread, with clinically important roles in SKELETAL MUSCLE; LIVER; and vascular, bronchial, gastrointestinal, and genitourinary SMOOTH MUSCLE. Adrenergic beta-2 Receptors,Receptors, beta-2 Adrenergic,beta-2 Adrenergic Receptors,Adrenergic Receptor, beta-2,Receptor, Adrenergic, beta-2,beta 2 Adrenergic Receptors,Adrenergic Receptor, beta 2,Adrenergic Receptors, beta-2,Adrenergic beta 2 Receptors,Receptor, beta-2 Adrenergic,Receptors, Adrenergic beta-2,Receptors, beta 2 Adrenergic,beta-2 Adrenergic Receptor,beta-2 Receptors, Adrenergic

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