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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Autores principales:	Miquel Saumell-Esnaola, Sergio Barrondo, Gontzal García del Caño, María Aranzazu Goicolea, Joan Sallés, Beat Lutz, Krisztina Monory
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	type 1 cannabinoid receptor CB1 cholesterol hippocampus frontal cortex synaptosomes rescue model Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/07b426a064de4ede87720ba85677203f
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spelling	oai:doaj.org-article:07b426a064de4ede87720ba85677203f2021-11-25T18:28:14ZSubsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex10.3390/molecules262268971420-3049https://doaj.org/article/07b426a064de4ede87720ba85677203f2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6897https://doaj.org/toc/1420-3049Numerous 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.Miquel Saumell-EsnaolaSergio BarrondoGontzal García del CañoMaría Aranzazu GoicoleaJoan SallésBeat LutzKrisztina MonoryMDPI AGarticletype 1 cannabinoid receptor CB1cholesterolhippocampusfrontal cortexsynaptosomesrescue modelOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6897, p 6897 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	type 1 cannabinoid receptor CB1 cholesterol hippocampus frontal cortex synaptosomes rescue model Organic chemistry QD241-441
spellingShingle	type 1 cannabinoid receptor CB1 cholesterol hippocampus frontal cortex synaptosomes rescue model Organic chemistry QD241-441 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
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.
format	article
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
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_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_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_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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/07b426a064de4ede87720ba85677203f
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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

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