title: Altered surface trafficking of presynaptic cannabinoid type 1 receptor in and out synaptic terminals parallels receptor desensitization.
abstract: Presynaptic cannabinoid type 1 receptors (CB1Rs) are major mediators of retrograde synaptic plasticity at both excitatory and inhibitory synapses and participate in a plethora of physiological functions. Whether presynaptic receptors, such as CB1R, display functionally relevant movements at the surface of neuronal membranes is not known. We analyzed the lateral mobility of native CB1Rs in cortical neurons by using single-quantum dot imaging. We found that CB1Rs are highly mobile and rapidly diffuse in and out of presynapses. Agonist-induced desensitization correlated with a reduction in the fraction of surface CB1Rs and a drastic decrease in the membrane dynamic of the CB1Rs that remained at the presynaptic surface. Desensitization specifically excluded CB1Rs from synapses and increased the fraction of immobile receptors in the extrasynaptic compartment. The results suggest that decrease of mobility may be one of the core mechanisms underlying the desensitization of CB1R, the most abundant G protein-coupled receptor in the brain.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U862 Laboratory Physiopathology of Synaptic Plasticity, Neurocentre Magendie, 146 rue Leo Saignat, 33077 Bordeaux, France.
authors.forename: Lenka
authors.initials: L
authors.lastname: Mikasova
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
authors.forename: Daniel
authors.initials: D
authors.lastname: Choquet
authors.forename: Olivier J
authors.initials: OJ
authors.lastname: Manzoni
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D017729:Presynaptic Terminals / Q000378:metabolism*; D021381:Protein Transport; D045663:Quantum Dots; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*
chemical_list: D043884:Receptor, Cannabinoid, CB1