Altered surface trafficking of presynaptic cannabinoid type 1 receptor in and out synaptic terminals parallels receptor desensitization
Proceedings of the National Academy of Sciences. 2008-11-17; 105(47): 18596-18601
DOI: 10.1073/pnas.0805959105
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1. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18596-601. doi:
10.1073/pnas.0805959105. Epub 2008 Nov 17.
Altered surface trafficking of presynaptic cannabinoid type 1 receptor in and out
synaptic terminals parallels receptor desensitization.
Mikasova L(1), Groc L, Choquet D, Manzoni OJ.
Author information:
(1)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.
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.
DOI: 10.1073/pnas.0805959105
PMCID: PMC2584146
PMID: 19015531 [Indexed for MEDLINE]