Stable G protein-effector complexes in striatal neurons: mechanism of assembly and role in neurotransmitter signaling
- The Scripps Research Institute, United States
- Nagasaki University, Japan
- Brigham Young University, United States
- Ewha Womans University, Republic of Korea
- The University of Texas Health Science Center, United States
- Icahn School of Medicine at Mount Sinai, United States
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.
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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.
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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Stable G protein-effector complexes in striatal neurons: mechanism of assembly and role in neurotransmitter signaling
eLife 4:e10451.
https://doi.org/10.7554/eLife.10451
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