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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RESEARCH PRODUCT

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.

Joan Sallés Miquel Saumell-esnaola Miquel Saumell-esnaola Gontzal García Del Caño Sergio Barrondo M.a. Goicolea Beat Lutz Krisztina Monory

subject

Cannabinoid receptor G protein hippocampus Pharmaceutical Science Hippocampus Organic chemistry anti-CB1 antibody GTP-Binding Protein alpha Subunits Gi-Go Inhibitory postsynaptic potential Article rescue model Analytical Chemistry Glutamatergic Mice QD241-441 Membrane Microdomains Receptor Cannabinoid CB1 Drug Discovery type 1 cannabinoid receptor CB1 Animals Physical and Theoretical Chemistry Lipid raft Mice Knockout Chemistry frontal cortex musculoskeletal neural and ocular physiology food and beverages cholesterol synaptosomes Endocannabinoid system Cell biology Frontal Lobe nervous system Chemistry (miscellaneous)Synapses Molecular Medicine GABAergic lipids (amino acids peptides and proteins)psychological phenomena and processes Signal Transduction

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. This research was funded by the Basque Government (IT1230-19), MINECO, Spanish Ministry of Science, Innovation and Universities (CTQ2017-85686-R).

year	journal	country	edition	language
2021-11-16	Molecules (Basel, Switzerland)

10.3390/molecules26226897 https://pubmed.ncbi.nlm.nih.gov/34833992