1. Cell Biology
  2. Neuroscience
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Olfactory receptor accessory proteins play crucial roles in receptor function and gene choice

  1. Ruchira Sharma
  2. Yoshiro Ishimaru
  3. Ian G Davison
  4. Kentaro Ikegami
  5. Ming-Shan Chien
  6. Helena You
  7. Qiuyi Chi
  8. Momoka Kubota
  9. Masafumi Yohda
  10. Michael Ehlers
  11. Hiroaki Matsunami  Is a corresponding author
  1. Duke University Medical Center, United States
  2. Tokyo University of Agriculture and Technology, Japan
Research Article
  • Cited 15
  • Views 3,159
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Cite this article as: eLife 2017;6:e21895 doi: 10.7554/eLife.21895

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. 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.

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Author details

  1. Ruchira Sharma

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2795-7457
  2. Yoshiro Ishimaru

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ian G Davison

    Department of Neurobiology, Duke University Medical Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0998-7676
  4. Kentaro Ikegami

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ming-Shan Chien

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Helena You

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Qiuyi Chi

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Momoka Kubota

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Masafumi Yohda

    Tokyo University of Agriculture and Technology, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  10. Michael Ehlers

    Department of Neurobiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Hiroaki Matsunami

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    For correspondence
    hiroaki.matsunami@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8850-2608

Funding

National Institutes of Health (R01 DC014423)

  • Hiroaki Matsunami

National Institutes of Health (R01 DC012095)

  • Hiroaki Matsunami

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (A161-16-07) of the Duke Animal Care and Use program.

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: September 28, 2016
  2. Accepted: February 16, 2017
  3. Accepted Manuscript published: March 6, 2017 (version 1)
  4. Version of Record published: March 22, 2017 (version 2)

Copyright

© 2017, Sharma et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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