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

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 or...

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Bibliographic Details
Published in:eLife 2015-11, Vol.4
Main Authors: Xie, Keqiang, Masuho, Ikuo, Shih, Chien-Cheng, Cao, Yan, Sasaki, Keita, Lai, Chun Wan J, Han, Pyung-Lim, Ueda, Hiroshi, Dessauer, Carmen W, Ehrlich, Michelle E, Xu, Baoji, Willardson, Barry M, Martemyanov, Kirill A
Format: Article
Language:English
Subjects:
Acoustics
Adenosine
Adenylyl Cyclases - metabolism
Animal models
Animals
cAMP
Cell Biology
Cellular signal transduction
Corpus striatum
Cyclic AMP
G protein
G protein-coupled receptors
G proteins
GTP-Binding Protein alpha Subunits - metabolism
Mice
motor control
Motor skill learning
Motor task performance
Neostriatum
Neurological research
Neurons - enzymology
Neuroscience
Neurotransmitter Agents - metabolism
Neurotransmitter receptors
Neurotransmitters
Pharmacology
Physiological aspects
Protein Multimerization
Proteins
Receptors, Neurotransmitter - metabolism
signal transduction
striatum
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.10451