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

Keqiang Xie, Ikuo Masuho, Chien Cheng Shih, Yan Cao, Keita Sasaki, Chun Wan J. Lai, Pyung Lim Han, Hiroshi Ueda, Carmen W. Dessauer, Michelle E. Ehrlich, Baoji Xu, Barry M. Willardson, Kirill A. Martemyanov

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish
Article numbere10451
Pages (from-to)1-21
Number of pages21
JournaleLife
Volume4
Issue numberNOVEMBER2015
DOIs
StatePublished - 27 Nov 2015

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