GPCRs promote the release of zinc ions mediated by nNOS/NO and the redox transducer RGSZ2 protein

Antioxidants & Redox Signaling
Pilar Sánchez-BlázquezJavier Garzón

Abstract

Morphine signaling via the μ-opioid receptor (MOR) is coupled to redox-dependent zinc release from endogenous stores. Thus, MOR activation stimulates the complex formed by RGSZ2 (a regulator of G protein signaling) and neural nitric oxide synthase (nNOS) to produce NO, and to recruit PKCγ and Raf-1 in a zinc-dependent manner. Accordingly, we investigated whether redox regulation of zinc metabolism was unique to the MOR, or if it is a signaling mechanism shared by G-protein coupled receptors (GPCRs). A physical interaction with the RGSZ2-nNOS complex was detected for the following GPCRs: neuropeptides, MOR and δ-opioid (DOR); biogenic amines, 5HT1A, 5HT2A, α2A, D1 and D2; acetylcholine, muscarinic M2 and M4; excitatory amino acid glutamate, mGlu2 and mGlu5; and derivatives of arachidonic acid (anandamide), CB1. Agonist activation of these receptors induced the release of zinc ions from the RGSZ2 zinc finger via a nNOS/NO-dependent mechanism, recruiting PKCγ and Raf-1 to the C terminus or the third internal loop of the GPCR. A series of GPCRs share an unexpected mechanistic feature, the nNOS/NO-dependent regulation of zinc ion signaling via a redox mechanism. The RGSZ2 protein emerges as a potential redox zinc switch that convert...Continue Reading

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Citations

May 15, 2013·Molecular Neurobiology·María Rodríguez-Muñoz, Javier Garzón
Jun 6, 2013·Future Medicinal Chemistry·Christopher R BodleDavid L Roman
Aug 29, 2013·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Zhelong Xu, Juan Zhou
Aug 25, 2015·Neuroscience Letters·Yong-Hui DangCheng-Ge Gao
Nov 20, 2015·Antioxidants & Redox Signaling·Ana I CasasHarald H H W Schmidt
Sep 11, 2012·Free Radical Biology & Medicine·Patricia I Oteiza
Dec 3, 2014·Neuropharmacology·Javier GarzónPilar Sánchez-Blázquez
Jan 6, 2015·Antioxidants & Redox Signaling·María Rodríguez-MuñozJavier Garzón
May 16, 2019·Antioxidants & Redox Signaling·Elsa Cortés-MonteroJavier Garzón
Mar 15, 2020·Addiction Biology·Peng LiuYong-Hui Dang
Dec 8, 2017·Neural Plasticity·Peng LiuYonghui Dang
Mar 27, 2015·Molecular Pharmacology·Henry A Dunn, Stephen S G Ferguson

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Methods Mentioned

BETA
PMA
bimolecular fluorescence complementation
chip
surface plasmon resonance
confocal microscopy
immunoprecipitation
electrophoresis
transgenic
protein kinase C assay

Software Mentioned

SigmaStat
SPSS
BIAevaluation

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