NDLI: Zinc Is Involved in Depression by Modulating G Protein-Coupled Receptor Heterodimerization

Content Provider	Springer Nature Link
Author	Tena Campos, Mercè Ramon, Eva Lupala, Cecylia S. Pérez, Juan J. Koch, Karl W. Garriga, Pere
Copyright Year	2015
Abstract	5-Hydroxytryptamine 1A receptor and galanin receptor 1 belong to the G protein-coupled receptors superfamily, and they have been described to heterodimerize triggering an anomalous physiological state that would underlie depression. Zinc supplementation has been widely reported to improve treatment against major depressive disorder. Our work has focused on the study and characterization of these receptors and its relationships with zinc both under purified conditions and in cell culture. To this aim, we have designed a strategy to purify the receptors in a conformationally active state. We have used receptors tagged with the monoclonal Rho-1D4 antibody and employed ligand-assisted purification in order to successfully purify both receptors in a properly folded and active state. The interaction between both purified receptors has been analyzed by surface plasmon resonance in order to determine the kinetics of dimerization. Zinc effect on heteromer has also been tested using the same methodology but exposing the 5-hydroxytryptamine 1A receptor to zinc before the binding experiment. These results, combined with Förster resonance energy transfer (FRET) measurements, in the absence and presence of zinc, suggest that this ion is capable of disrupting this interaction. Moreover, molecular modeling suggests that there is a coincidence between zinc-binding sites and heterodimerization interfaces for the serotonin receptor. Our results establish a rational explanation for the role of zinc in the molecular processes associated with receptor-receptor interactions and its relationship with depression, in agreement with previously reported evidence for the positive effects of zinc in depression treatment, and the involvement of our target dimer in the same disease.
Starting Page	2003
Ending Page	2015
Page Count	13
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	3
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-04-09
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	G protein-coupled receptor Heterodimerization Protein stability Purified receptor Galanin receptor Serotonin receptor G protein signaling Zinc Depression Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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