title: Olfactory receptor accessory proteins play crucial roles in receptor function and gene choice.
abstract: Each of the olfactory sensory neurons (OSNs) chooses to express a single G protein-coupled olfactory receptor (OR) from a pool of hundreds. Here, we show the receptor transporting protein (RTP) family members play a dual role in both normal OR trafficking and determining OR gene choice probabilities.Rtp1andRtp2double knockout mice (RTP1,2DKO) show OR trafficking defects and decreased OSN activation. Surprisingly, we discovered a small subset of the ORs are expressed in larger numbers of OSNs despite the presence of fewer total OSNs in RTP1,2DKO. Unlike typical ORs, some overrepresented ORs show robust cell surface expression in heterologous cells without the co-expression of RTPs. We present a model in which developing OSNs exhibit unstable OR expression until they choose to express an OR that exits the ER or undergo cell death. Our study sheds light on the new link between OR protein trafficking and OR transcriptional regulation.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States.
authors.forename: Ruchira
authors.identifier: 0000-0002-2795-7457
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States.|Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ishimaru
authors.affiliation: Department of Biology, Boston University, Boston, United States.
authors.forename: Ian
authors.identifier: 0000-0003-0998-7676
authors.initials: I
authors.lastname: Davison
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States.|Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ikegami
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States.
authors.forename: Ming-Shan
authors.initials: MS
authors.lastname: Chien
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States.
authors.forename: Helena
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States.
authors.forename: Quiyi
authors.initials: Q
authors.lastname: Chi
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States.
authors.forename: Momoka
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yohda
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, United States.|Biogen Inc, Cambridge, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Ehlers
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States.|Department of Neurobiology, Duke University Medical Center, Durham, United States.|Duke Institute for Brain Sciences, Durham, United States.
authors.forename: Hiroaki
authors.identifier: 0000-0002-8850-2608
authors.initials: H
authors.lastname: Matsunami
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D018345:Mice, Knockout; D008954:Models, Biological; D018035:Receptors, Odorant / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018035:Receptors, Odorant
keywords: GPCR; UPR; cell biology; chaperone; epigenetic; gene regulation; mouse; neuroscience; odorant; olfaction; unfolded protein response