title: Ric-8B, an olfactory putative GTP exchange factor, amplifies signal transduction through the olfactory-specific G-protein Galphaolf.
abstract: The olfactory system is able to detect a large number of chemical structures with a remarkable sensitivity and specificity. Odorants are first detected by odorant receptors present in the cilia of olfactory neurons. The activated receptors couple to an olfactory-specific G-protein (Golf), which activates adenylyl cyclase III to produce cAMP. Increased cAMP levels activate cyclic nucleotide-gated channels, causing cell membrane depolarization. Here we used yeast two-hybrid to search for potential regulators for Galphaolf. We found that Ric-8B (for resistant to inhibitors of cholinesterase), a putative GTP exchange factor, is able to interact with Galphaolf. Like Galphaolf, Ric-8B is predominantly expressed in the mature olfactory sensory neurons and also in a few regions in the brain. The highly restricted and colocalized expression patterns of Ric-8B and Galphaolf strongly indicate that Ric-8B is a functional partner for Galphaolf. Finally, we show that Ric-8B is able to potentiate Galphaolf-dependent cAMP accumulation in human embryonic kidney 293 cells and therefore may be an important component for odorant signal transduction.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Luiz Eduardo C
authors.initials: LE
authors.lastname: Von Dannecker
authors.forename: Adriana F
authors.initials: AF
authors.lastname: Mercadante
authors.forename: Bettina
authors.initials: B
authors.lastname: Malnic
mesh_terms: D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000172:deficiency / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis / Q000502:physiology; D009687:Nuclear Proteins / Q000494:pharmacology / Q000502:physiology*; D009831:Olfactory Mucosa / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection / Q000379:methods; D020798:Two-Hybrid System Techniques; D015003:Yeasts
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; C485884:Ric8a protein, mouse; C559967:Ric8b protein, mouse; C084618:olfactory G protein subunit alpha olf; D000242:Cyclic AMP