Expression of Melatonin and Dopamine D Receptor Heteromers in Eye Ciliary Body Epithelial Cells and Negative Correlation with Ocular Hypertension
Reyes-Resina, Irene (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Awad Alkozi, Hanan (University Complutense of Madrid. Faculty of Optics and Optometry. Department of Biochemistry)
del Ser Badia, Anna (Universitat Autònoma de Barcelona. Institut de Neurociències)
Sánchez-Naves, Juan (Institut d'Oftalmologia de les Illes Balears)
Lillo, Jaume (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Jiménez, Jasmina (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Pintor, Jesús (University Complutense of Madrid. Faculty of Optics and Optometry. Department of Biochemistry and Molecular Biology)
Navarro Brugal, Gemma (Universitat de Barcelona. Departament de Bioquímica i Fisiologia)
Franco, Rafael (Universitat de Barcelona. Facultat de Química)
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Date:	2020
Abstract:	Background: Experiments in the late nineties showed an inverse relationship in the eye levels of melatonin and dopamine, thereby constituting an example of eye parameters that are prone to circadian variations. The underlying mechanisms are not known but these relevant molecules act via specific cell surface dopamine and melatonin receptors. This study investigated whether these receptors formed heteromers whose function impact on eye physiology. We performed biophysical assays to identify interactions in heterologous systems. Particular heteromer functionality was detected using Gi coupling, MAPK activation, and label-free assays. The expression of the heteroreceptor complexes was assessed using proximity ligation assays in cells producing the aqueous humor and human eye samples. Dopamine D receptors (DRs) were identified in eye ciliary body epithelial cells. We discovered heteromers formed by DR and either MT (MTR) or MT (MTR) melatonin receptors. Heteromerization led to the blockade of DR-Gi coupling and regulation of signaling to the MAPK pathway. Heteromer expression was negatively correlated with intraocular hypertension. Conclusions: Heteromers likely mediate melatonin and dopamine actions in structures regulating intraocular pressure. Significant expression of DR-MTR and DR-MTR was associated with normotensive conditions, whereas expression diminished in a cell model of hypertension. A clear trend of expression reduction was observed in samples from glaucoma cases. The trend was marked but no statistical analysis was possible as the number of available eyes was 2.
Grants:	Ministerio de Economía y Competitividad SAF2013-44416-R Ministerio de Economía y Competitividad SAF2016-77084-R Ministerio de Economía y Competitividad BFU2015-64405-R
Note:	Altres ajuts: MINS/RETICS/RD12/0034/0003
Note:	Altres ajuts: MINS/RETICS/RD16/0008/0017
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Circadian rhythm ; Glaucoma ; G-protein-coupled receptor GPCR heteromer ; Melatonin MT and MT receptors ; G protein coupling ; Mitogen-activated protein kinase pathway (MAPK) ; Label-free dynamic mass redistribution (DMR) ; Retina ; Human 59HCE cells
Published in:	Cells, Vol. 9, Num. 1 (January 2020) , art. 152, ISSN 2073-4409

DOI: 10.3390/cells9010152
PMID: 31936298

20 p, 3.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles