Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex

Numerous studies have investigated the roles of the type 1 cannabinoid receptor (CB1) in glutamatergic and GABAergic neurons. Here, we used the cell-type-specific CB1 rescue model in mice to gain insight into the organizational principles of plasma membrane targeting and Gαi/o protein signalling of...

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Main Authors: Miquel Saumell-Esnaola, Sergio Barrondo, Gontzal García del Caño, María Aranzazu Goicolea, Joan Sallés, Beat Lutz, Krisztina Monory
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/22/6897
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author Miquel Saumell-Esnaola
Sergio Barrondo
Gontzal García del Caño
María Aranzazu Goicolea
Joan Sallés
Beat Lutz
Krisztina Monory
author_facet Miquel Saumell-Esnaola
Sergio Barrondo
Gontzal García del Caño
María Aranzazu Goicolea
Joan Sallés
Beat Lutz
Krisztina Monory
author_sort Miquel Saumell-Esnaola
collection DOAJ
description Numerous studies have investigated the roles of the type 1 cannabinoid receptor (CB1) in glutamatergic and GABAergic neurons. Here, we used the cell-type-specific CB1 rescue model in mice to gain insight into the organizational principles of plasma membrane targeting and Gαi/o protein signalling of the CB1 receptor at excitatory and inhibitory terminals of the frontal cortex and hippocampus. By applying biochemical fractionation techniques and Western blot analyses to synaptosomal membranes, we explored the subsynaptic distribution (pre-, post-, and extra-synaptic) and CB1 receptor compartmentalization into lipid and non-lipid raft plasma membrane microdomains and the signalling properties. These data infer that the plasma membrane partitioning of the CB1 receptor and its functional coupling to Gαi/o proteins are not biased towards the cell type of CB1 receptor rescue. The extent of the canonical Gαi/o protein-dependent CB1 receptor signalling correlated with the abundance of CB1 receptor in the respective cell type (glutamatergic versus GABAergic neurons) both in frontal cortical and hippocampal synaptosomes. In summary, our results provide an updated view of the functional coupling of the CB1 receptor to Gαi/o proteins at excitatory and inhibitory terminals and substantiate the utility of the CB1 rescue model in studying endocannabinoid physiology at the subcellular level.
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spelling doaj.art-07b426a064de4ede87720ba85677203f2023-11-23T00:35:26ZengMDPI AGMolecules1420-30492021-11-012622689710.3390/molecules26226897Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal CortexMiquel Saumell-Esnaola0Sergio Barrondo1Gontzal García del Caño2María Aranzazu Goicolea3Joan Sallés4Beat Lutz5Krisztina Monory6Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainDepartment of Pharmacology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainBioaraba, Neurofarmacología Celular y Molecular, 01009 Vitoria-Gasteiz, SpainDepartment of Analytical Chemistry, Faculty of Pharmacy, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainDepartment of Pharmacology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, SpainInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, GermanyInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, GermanyNumerous studies have investigated the roles of the type 1 cannabinoid receptor (CB1) in glutamatergic and GABAergic neurons. Here, we used the cell-type-specific CB1 rescue model in mice to gain insight into the organizational principles of plasma membrane targeting and Gαi/o protein signalling of the CB1 receptor at excitatory and inhibitory terminals of the frontal cortex and hippocampus. By applying biochemical fractionation techniques and Western blot analyses to synaptosomal membranes, we explored the subsynaptic distribution (pre-, post-, and extra-synaptic) and CB1 receptor compartmentalization into lipid and non-lipid raft plasma membrane microdomains and the signalling properties. These data infer that the plasma membrane partitioning of the CB1 receptor and its functional coupling to Gαi/o proteins are not biased towards the cell type of CB1 receptor rescue. The extent of the canonical Gαi/o protein-dependent CB1 receptor signalling correlated with the abundance of CB1 receptor in the respective cell type (glutamatergic versus GABAergic neurons) both in frontal cortical and hippocampal synaptosomes. In summary, our results provide an updated view of the functional coupling of the CB1 receptor to Gαi/o proteins at excitatory and inhibitory terminals and substantiate the utility of the CB1 rescue model in studying endocannabinoid physiology at the subcellular level.https://www.mdpi.com/1420-3049/26/22/6897type 1 cannabinoid receptor CB1cholesterolhippocampusfrontal cortexsynaptosomesrescue model
spellingShingle Miquel Saumell-Esnaola
Sergio Barrondo
Gontzal García del Caño
María Aranzazu Goicolea
Joan Sallés
Beat Lutz
Krisztina Monory
Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex
Molecules
type 1 cannabinoid receptor CB1
cholesterol
hippocampus
frontal cortex
synaptosomes
rescue model
title Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex
title_full Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex
title_fullStr Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex
title_full_unstemmed Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex
title_short Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex
title_sort subsynaptic distribution lipid raft targeting and g protein dependent signalling of the type 1 cannabinoid receptor in synaptosomes from the mouse hippocampus and frontal cortex
topic type 1 cannabinoid receptor CB1
cholesterol
hippocampus
frontal cortex
synaptosomes
rescue model
url https://www.mdpi.com/1420-3049/26/22/6897
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