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

doi:10.7554/eLife.10451

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

Divison of Brain & Cognitive Sciences

Research output: Contribution to journal › Article › peer-review

27 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 G_olf. However, the molecular organization of the G_olf-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 G_olf heterotrimer. We use genetic mouse models with disruption in individual components of the complex to reveal hierarchical order of interactions required for AC5-G_olf stability. We further identify that the assembly of AC5-G_olf 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 language	English
Article number	e10451
Pages (from-to)	1-21
Number of pages	21
Journal	eLife
Volume	4
Issue number	NOVEMBER2015
DOIs	https://doi.org/10.7554/eLife.10451
State	Published - 27 Nov 2015

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Xie, K., Masuho, I., Shih, C. C., Cao, Y., Sasaki, K., Lai, C. W. J., Han, P. L., Ueda, H., Dessauer, C. W., Ehrlich, M. E., Xu, B., Willardson, B. M., & Martemyanov, K. A. (2015). Stable G protein-effector complexes in striatal neurons: Mechanism of assembly and role in neurotransmitter signaling. eLife, 4(NOVEMBER2015), 1-21. Article e10451. https://doi.org/10.7554/eLife.10451

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

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.",

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

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AU - Cao, Yan

AU - Sasaki, Keita

AU - Lai, Chun Wan J.

AU - Han, Pyung Lim

AU - Ueda, Hiroshi

AU - Dessauer, Carmen W.

AU - Ehrlich, Michelle E.

AU - Xu, Baoji

AU - Willardson, Barry M.

AU - Martemyanov, Kirill A.

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

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