Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Yoshiro Ishimaru
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
Department of Biology, Boston University, Boston, United States
Kentaro Ikegami
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States; Tokyo University of Agriculture and Technology, Tokyo, Japan
Ming-Shan Chien
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Helena You
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Quiyi Chi
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Momoka Kubota
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Masafumi Yohda
Tokyo University of Agriculture and Technology, Tokyo, Japan
Michael Ehlers
Department of Neurobiology, Duke University Medical Center, Durham, United States; Biogen Inc, Cambridge, United States
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
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. Rtp1 and Rtp2 double 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.
