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.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, United States.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, United States.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Masuho
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, United States.|Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, United States.
authors.forename: Chien-Cheng
authors.initials: CC
authors.lastname: Shih
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, United States.
authors.forename: Chun Wan J
authors.initials: CW
authors.lastname: Lai
authors.affiliation: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Pyung-Lim
authors.initials: PL
authors.lastname: Han
authors.affiliation: Department of Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, United States.
authors.forename: Carmen W
authors.initials: CW
authors.lastname: Dessauer
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States.|Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, United States.|Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Ehrlich
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, United States.
authors.forename: Baoji
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, United States.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Willardson
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, United States.
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Martemyanov
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000201:enzymology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D055503:Protein Multimerization; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; C084618:olfactory G protein subunit alpha olf; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V
keywords: G proteins; cAMP; cell biology; motor control; mouse; neuroscience; signal transduction; striatum