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

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
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: Online
Language:English
Published: eLife Sciences Publications, Ltd 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728126/
Description
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.

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