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Elife. 2015 Nov 27;4. pii: e10451. doi: 10.7554/eLife.10451.

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

Author information

1
Department of Neuroscience, The Scripps Research Institute, Jupiter, United States.
2
Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, United States.
3
Department of Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
4
Department of Chemistry and Biochemistry, Brigham Young University, Provo, United States.
5
Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, Republic of Korea.
6
Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, United States.
7
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States.
8
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, United States.
9
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, 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.

KEYWORDS:

G proteins; cAMP; cell biology; motor control; mouse; neuroscience; signal transduction; striatum

PMID:
26613416
PMCID:
PMC4728126
DOI:
10.7554/eLife.10451
[Indexed for MEDLINE]
Free PMC Article

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