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Mechanisms of Biased β-Arrestin-Mediated Signaling Downstream from the Cannabinoid 1 Receptor

Year: 2016
Type: article
Abstract: Activation of G protein-coupled receptors results in multiple waves of signaling that are mediated by heterotrimeric G proteins and the scaffolding proteins β-arrestin 1/2. Ligands can elicit full or subsets of cellular responses, a concept defined as ligand bias or functional selectivity. However, our current understanding of β-arrestin-mediated signaling is still very limited. Here we provide a comprehensive view of β-arrestin-mediated signaling from the cannabinoid 1 receptor (CB1R). By using a signaling biased receptor, we define the cascades, specific receptor kinases, and molecular mechanism underlying β-arrestin-mediated signaling: We identify the interaction kinetics of CB1R and β-arrestin 1 during their endocytic trafficking as directly proportional to its efficacy. Finally, we demonstrate that signaling results in the control of genes clustered around prosurvival and proapoptotic functions among others. Together, these studies constitute a comprehensive description of β-arrestin-mediated signaling from CB1Rs and suggest modulation of receptor endocytic trafficking as a therapeutic approach to control β-arrestin-mediated signaling.
DOI: 10.1124/mol.115.103176
Authors: Francheska Delgado-Peraza, Kwang H. Ahn, Carlos Nogueras-Ortiz, Imran N. Mungrue, Ken Mackie, Debra A. Kendall, Guillermo A. Yudowski
Institutions: University of Connecticut, University of Puerto Rico, Medical Sciences Campus, University of Puerto Rico System, Indiana University Bloomington, Indiana University, Louisiana State University Health Sciences Center New Orleans
Language: English
Open Access status: hybrid
Estimated APC paid: $3,600
Funders: National Science Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute on Minority Health and Health Disparities
Awards: G1091189484, Regulation of GPCR Recycling at the Plasma Membrane, G193213942, G194171315, G2059395873, G246225891, G312437830, G3265888792, G4986506763, Determining roles of the pro-apoptotic UPR gene CHAC1 in atherosclerosis., REU Site: Research Experiences for Underrepresented Minority Undergraduates in Basica and Genetic Research at Louisiana State University Health Sciences Center (LSUHSC), MRI: Procurement of a Shared Confocal Microscope Facility at the Institute of Neurobiology, G6685671204, Determining roles of the pro-apoptotic UPR gene CHAC1 in atherosclerosis., G886786700, G9000043731, G9000074285, G9000079884, G9000110348, G9000125415, G9000208972, G9000279387, G9000319048, G979614752
OpenAlex ID: W2306894756
FWCI: 5.869
Cites: 65
Cited by: 95
Related to: 10