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Article

Electron Paramagnetic Resonance Gives Evidence for the Presence of Type 1 Gonadotropin-Releasing Hormone Receptor (GnRH-R) in Subdomains of Lipid Rafts

1
Laboratory of Biophysics, Department of Condensed Matter Physics, Jožef Stefan Institute, 1000 Ljubljana, Slovenia
2
Veterinary Faculty, Institute of Preclinical Sciences, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia
3
Research Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences, Hospital del Mar Medical Research Institute (IMIM), Pompeu Fabra University (UPF), 08003 Barcelona, Spain
4
Laboratory of Biomolecular Research, Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland
5
Condensed Matter Theory Group, PSI, 5232 Villigen, Switzerland
6
Faculty of Medicine, Institute of Biochemistry and Molecular Genetics, University of Ljubljana, 1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Current address: Pride Veterinary Centre, Riverside Road, Derby DE24 8HX, UK.
Academic Editor: Diego Muñoz-Torrero
Molecules 2021, 26(4), 973; https://doi.org/10.3390/molecules26040973
Received: 15 January 2021 / Revised: 2 February 2021 / Accepted: 8 February 2021 / Published: 12 February 2021
(This article belongs to the Special Issue G Protein-Coupled Receptors)
This study investigated the effect of type 1 gonadotropin releasing hormone receptor (GnRH-R) localization within lipid rafts on the properties of plasma membrane (PM) nanodomain structure. Confocal microscopy revealed colocalization of PM-localized GnRH-R with GM1-enriched raft-like PM subdomains. Electron paramagnetic resonance spectroscopy (EPR) of a membrane-partitioned spin probe was then used to study PM fluidity of immortalized pituitary gonadotrope cell line αT3-1 and HEK-293 cells stably expressing GnRH-R and compared it with their corresponding controls (αT4 and HEK-293 cells). Computer-assisted interpretation of EPR spectra revealed three modes of spin probe movement reflecting the properties of three types of PM nanodomains. Domains with an intermediate order parameter (domain 2) were the most affected by the presence of the GnRH-Rs, which increased PM ordering (order parameter (S)) and rotational mobility of PM lipids (decreased rotational correlation time (τc)). Depletion of cholesterol by methyl-β-cyclodextrin (methyl-β-CD) inhibited agonist-induced GnRH-R internalization and intracellular Ca2+ activity and resulted in an overall reduction in PM order; an observation further supported by molecular dynamics (MD) simulations of model membrane systems. This study provides evidence that GnRH-R PM localization may be related to a subdomain of lipid rafts that has lower PM ordering, suggesting lateral heterogeneity within lipid raft domains. View Full-Text
Keywords: 7TM receptors; type 1 gonadotropin-releasing hormone receptor; plasma membrane; electron paramagnetic resonance (EPR); lipid rafts 7TM receptors; type 1 gonadotropin-releasing hormone receptor; plasma membrane; electron paramagnetic resonance (EPR); lipid rafts
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MDPI and ACS Style

Koklič, T.; Hrovat, A.; Guixà-González, R.; Rodríguez-Espigares, I.; Navio, D.; Frangež, R.; Uršič, M.; Kubale, V.; Plemenitaš, A.; Selent, J.; Šentjurc, M.; Vrecl, M. Electron Paramagnetic Resonance Gives Evidence for the Presence of Type 1 Gonadotropin-Releasing Hormone Receptor (GnRH-R) in Subdomains of Lipid Rafts. Molecules 2021, 26, 973. https://doi.org/10.3390/molecules26040973

AMA Style

Koklič T, Hrovat A, Guixà-González R, Rodríguez-Espigares I, Navio D, Frangež R, Uršič M, Kubale V, Plemenitaš A, Selent J, Šentjurc M, Vrecl M. Electron Paramagnetic Resonance Gives Evidence for the Presence of Type 1 Gonadotropin-Releasing Hormone Receptor (GnRH-R) in Subdomains of Lipid Rafts. Molecules. 2021; 26(4):973. https://doi.org/10.3390/molecules26040973

Chicago/Turabian Style

Koklič, Tilen, Alenka Hrovat, Ramon Guixà-González, Ismael Rodríguez-Espigares, Damaris Navio, Robert Frangež, Matjaž Uršič, Valentina Kubale, Ana Plemenitaš, Jana Selent, Marjeta Šentjurc, and Milka Vrecl. 2021. "Electron Paramagnetic Resonance Gives Evidence for the Presence of Type 1 Gonadotropin-Releasing Hormone Receptor (GnRH-R) in Subdomains of Lipid Rafts" Molecules 26, no. 4: 973. https://doi.org/10.3390/molecules26040973

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