Beta-arrestin signaling complex as a target for antidepressants and as a depression marker.
Beta-arrestins uncouple G protein-coupled receptors (GPCRs) from G proteins and promote their internalization, leading to desensitization and downregulation and serving as negative regulators of GPCR signaling. beta-Arrestins also function as scaffold proteins, interacting with several cytoplasmic proteins and linking GPCRs to intracellular signaling pathways such as the mitogen-activated protein kinase (MAPK) cascade. Recent work has also revealed that beta-arrestins translocate from the cytoplasm to the nucleus and associate with transcription factors such as histone acetyltransferase p300 and cyclic adenosine monophosphate (cAMP)-responsive element-binding protein. These substances also interact with regulators of transcription factors. We review findings on the effects of antidepressants on beta-arrestins and the plethora of antidepressant effects on signal transduction elements in which beta-arrestins serve as signaling scaffold proteins, focusing on the three major groups of MAPKs: extracellular signal-regulated kinases, c-Jun N-terminal kinases and p38 MAPKs, and on transcription factors and cofactors of which beta-arrestins mediate transcription regulation.
Schreiber
Gabriel
G
Department of Psychiatry of Ben Gurion University of the Negev, Beer Sheva, Israel.
Golan
Moran
M
Avissar
Sofia
S
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019390:Arrestins / Q000187:drug effects* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D016503:Drug Delivery Systems; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071557:beta-Arrestins
D000928:Antidepressive Agents; D019390:Arrestins; D015415:Biomarkers; D000071557:beta-Arrestins; D020928:Mitogen-Activated Protein Kinases