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Stable G protein-effector complexes in striatal neurons: mechanism of assembly and role in neurotransmitter signaling

  1. Keqiang Xie
  2. Ikuo Masuho
  3. Chien-Cheng Shih
  4. Yan Cao
  5. Keita Sasaki
  6. Chun Wan J Lai
  7. Pyung-Lim Han
  8. Hiroshi Ueda
  9. Carmen W Dessauer
  10. Michelle E Ehrlich
  11. Baoji Xu
  12. Barry M Willardson
  13. Kirill A Martemyanov  Is a corresponding author
  1. The Scripps Research Institute, United States
  2. Nagasaki University, Japan
  3. Brigham Young University, United States
  4. Ewha Womans University, Republic of Korea
  5. The University of Texas Health Science Center, United States
  6. Icahn School of Medicine at Mount Sinai, United States
Research Article
  • Cited 16
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Cite this article as: eLife 2015;4:e10451 doi: 10.7554/eLife.10451

Abstract

In the striatum, signaling via G protein-coupled neurotransmitter receptors is essential for motor control. Critical to this process is the effector enzyme adenylyl cyclase type 5 (AC5) that produces second messenger cAMP upon receptor-mediated activation by G protein Golf. However, the molecular organization of the Golf-AC5 signaling axis is not well understood. In this study, we report that in the striatum AC5 exists in a stable pre-coupled complex with subunits of Golf heterotrimer. We use genetic mouse models with disruption in individual components of the complex to reveal hierarchical order of interactions required for AC5-Golf stability. We further identify that the assembly of AC5-Golf complex is mediated by PhLP1 chaperone that plays central role in neurotransmitter receptor coupling to cAMP production motor learning. These findings provide evidence for the existence of stable G protein-effector signaling complexes and identify a new component essential for their assembly.

Article and author information

Author details

  1. Keqiang Xie

    Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ikuo Masuho

    Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Chien-Cheng Shih

    Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yan Cao

    Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Keita Sasaki

    Department of Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Chun Wan J Lai

    Department of Chemistry and Biochemistry, Brigham Young University, Provo, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Pyung-Lim Han

    Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  8. Hiroshi Ueda

    Department of Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Carmen W Dessauer

    Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Michelle E Ehrlich

    Departments of Neurology, Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Baoji Xu

    Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Barry M Willardson

    Department of Chemistry and Biochemistry, Brigham Young University, Provo, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Kirill A Martemyanov

    Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
    For correspondence
    kirill@scripps.edu
    Competing interests
    The authors declare that no competing interests exist.

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 procedures were approved by the Institutional Animal Care and Use Committee (IACUC) protocol (#14-001) at The Scripps Research Institute.

Reviewing Editor

  1. Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States

Publication history

  1. Received: July 29, 2015
  2. Accepted: November 26, 2015
  3. Accepted Manuscript published: November 27, 2015 (version 1)
  4. Version of Record published: December 31, 2015 (version 2)

Copyright

© 2015, Xie 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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